Conditioned Learning in Alcohol Dependence

British Journal of Addiction (1990) 85, 725-743
COMMENTARY
Conditioned learning in alcohol dependence:
implications for cue exposure treatment
D. COLIN DRUMMOND, TROY COOPER & STEVEN P. GLAUTIER
Addiction Research Unit, National Addition Centre, Institute of Psychiatry, 101 Denmark Hill,
London SE5 8AF, United Kingdom
Summary
A review of the literature pertinent to cue exposure treatment in alcohol dependence is presented. Psychological
models of relapse, based on conditioning and social learning theories, are critically evaluated. In particular,
attention is drawn to the potential implications for cue exposure research and treatment of an interaction
between Pavlovian and operant conditioning, problems with the application of the concepts of arousal and
craving and the importance of a systems model to understand physiological responses. It is concluded that no
study has so far demonstrated a link between conditioned responses to alcohol-related cues and relapse, an
assumption on which cue exposure treatment is based. Further, the evidence for the effectiveness of cue exposure
as a treatment is lacking. Promising research directions are identified.
Introduction
Wikler (1965) proposed a model of relapse of drug
use in abstinent opiate addicts which has inspired an
era of research into the effects of environmental
stimuli (or cues) on drug taking behaviour. He
suggested that environmental cues associated with
drug withdrawal come to elicit conditioned with-
drawal-like responses which precipitate further drug
use in the abstinent addict. He also suggested that
these conditioned responses (CRs) remain unaltered
by conventional addiction treatment. A later study
by Ludwig, Wikler & Stark (1974) which explored
the effects of exposure to alcohol related cues
(ARCs) in alcoholics, went further by concluding:
"Obviously any therapeutic approach, whether it
be insight, behaviourally or pharmacologically
orientated, that does not recognize the powerful,
evocative effects of interoceptive and exterocep-
tive stimuli. . . and that neglects to provide
techniques for modifying the strength of these
effects will likely be destined for failure" (p. 547)
While several authors have questioned the impor-
tance of CRs to environmental cues in the relapse
process (McAuliffe, 1982; Chaney, Roszell &
Cummings, 1982; Marlatt, 1985a) the numerous
studies which have explored the existence, signifi-
cance and modification of these responses in both
animals and humans attest to the impact which
Wikler's theory has had.
The technique of cue exposure, originally de-
scribed in relation to the treatment of cat phobia
(Freeman & Kendrick, 1960), has gained consider-
able popularity in the treatment of both phobic and
obsessive-compulsive neurosis (Marks, Hodgson &
Rachman, 1975). More recently cue exposure has
been applied to the treatment of alcohol and drug
dependence (Blakey & Baker, 1980; Rankin,
Hodgson & Stockwell, 1983; Laberg & EUertsen,
1987; McLellan et al., 1986) and owes much to this
and Wikler's early pioneering work. In comparison
to the neuroses, however, we argue that no study has
so far demonstrated that cue exposure has any
725
726 D. Colin Drummond, Troy Cooper & Steven P. Glautier
influence on clinical outcome in either alcohol or
drug dependence. This view stands in sharp contrast
to the optimistic views concerning the effectiveness
of cue exposure expressed by some authors.
Niaura et al. (1988) have provided a useful
review of some of the literature pertinent to
theoretical issues in cue exposure research and in
doing so, have stimulated considerable debate. This
paper aims to extend the debate into several
important areas which have not so far been consi-
dered. In order to orientate the reader there is some
overlap with Niaura et al. (1988) in terms of the
description of existing theoretical models, but im-
portant distinctions will be made in our interpreta-
tion of the evidence. In particular we draw attention
to the possible implications for cue exposure
research of an interaction between Pavlovian and
operant conditioning, problems with the application
of the concepts of arousal and craving and the
importance of applying a systems models to under-
stand physiological responsivity in cue exposure.
We argue that these issues have important implica-
tions for cue exposure treatment and suggest new
directions in which research could usefully be
directed.
While reference will be made to comparable
research in the opiate dependence field, this review
is largely restricted to the alcohol literature. We feel
that the diversity of the literature in the two fields
combined, would confuse rather than clarify the
issues involved. Having restricted the scope of the
paper in this way however, many of the theoretical
issues raised here may have direct relevance to cue
exposure in opiate dependence.
The paper is divided into two main sections. In
the first section we will compare the competing
psychological models which have been invoked to
explain the process of relapse, exploring their
possible relationship to cue exposure as a treatment
method. In doing so we intend to alert the reader to
sources of conceptual confusion and identify impor-
tant and so far unanswered theoretical questions
which serve to restrict further progress in cue
exposure research. The second section is focused on
the experimental evidence for the existence of
conditioned respones (CRs) to alcohol-related cues
(ARCs) in dependent and non-dependent drinkers
and provides a critique of studies utilizing cue
exposure as a treatment technique.
It is suggested that while subjective and psycho-
physiological responses to ARCs have been identi-
fied, their exact nature and interrelationship is
uncertain. Further, the relationship between CRs to
ARCs and relapse has yet to be conclusively
established. We intend to show that while cue
exposure is a promising approach to the treatment of
drug and alcohol dependence it's effectiveness has
not so far been demonstrated.
Competing models of relapse
Conditioned responses in relapse
The importance of conditioned responses to envi-
ronmental stimuli in the process of relapse was
asserted by Wikler (1965). This was based on his
observation that heroin addicts tended to return to
drug use even after months of abstinence when
exposed to an environment in which drug use had
previously taken place. This appeared to be due to
the re-emergence of withdrawal symptoms which
could not be attributed to elimination of the drug
from the body. He suggested that formerly neutral
environmental stimuli become associated with the
unconditioned stimulus (UCS) of a declining drug
plasma level which leads to the unconditioned
response of withdrawal symptoms (UCR) (see Fig.
1). These environmental stimuli (or cues) become
conditioned stimuli (CSs) which, when presented in
the absence of the UCS, invoke a conditioned
withdrawal response (CR).
Declining plasma
drug level
(UCS)
Environmental
Stimuli (cues)
(CS)
. Withdrawal
Symptoms
(UCR)
> Conditioned
Withdrawal
(CR)
Figure 1. Model of conditioned withdrawal.
According to this model, the connection between
a conditioned withdrawal response and relapse is
that drug use is motivated by the relief or avoidance
of withdrawal symptoms which are aversive in
nature. In effect, aversive CRs to ARCs act as
discriminative stimuli (SDs) for operant drinking
behaviour. While it should be noted that Wikler
later acknowledged that these CRs may be, in some
cases, drug-like and that drug taking may also be
motivated by the pursuit of positive hedonic effects
of the drug, this early theory remains popular with
contemporary researchers in the cue exposure field
(Pomerleau, 1981; Melchior & Tabakoff, 1984;
McLellan et al., 1986; Laberg & EUertsen, 1987;
Dolinsky et al, 1987; Bradley & Moorey, 1988).
Siegel has proposed an alternative explanation of
the observed phenomenon of CRs to drug cues (for
Cue exposure treatment in alcohol dependence 727
a review see Siegel, 1988). He argues that environ-
mental stimuli which precede drug administration,
rather than follow drug withdrawal, come to elicit
drug compensatory (or antagonistic) CRs which
oppose the unconditioned effects of the drug and
thus account for the development of tolerance.
Subsequent animal research has demonstrated con-
ditioned antagonistic responses to the analgesic
(Siegel, 1975; Krank et al., 1981), thermic (Siegel,
1978), sedating (Hinson & Siegel, 1983), gastroin-
testinal (Raffa et al, 1982) and lethal (Siegel et al,
1979) effects of morphine. Similarly, conditioned
antagonistic respones have been demonstrated in
animals to the hypothermic (Le et al, 1979;
Mansfield & Cunningham, 1980; Crowell et al,
1981) hypnotic (Melchior & Tabakoff, 1981) and
lethal (Melchior & Tabakoff, 1982) effects of
ethanol.
It would appear that the distinction between
models of Siegel and Wikler lies in the temporal
relationship between the cues and the unconditioned
effects of the drug. In reality this distinction is
extremely difficult to make, in that drug cues are
often present both during withdrawal and for some
time after the onset of drug agonist effects when an
individual takes a drug whilst experiencing with-
drawal. What is perhaps of greater importance is
that both models predict CRs which are opposite in
direction to the unconditioned drug effects.
Several studies have identified conditioned agon-
istic responses to drug cues (for a review see
Eikelboom & Stewart, 1982). Eikelboom & Stewart
(1982) suggest that the main factor which deter-
mines the direction of the CR to drug cues is the site
of drug action. Drugs which act on the efferent limb
of the central nervous system tend to produce
antagonistic responses, whereas drugs acting on the
afferent limb lead to conditioned agonistic responses
to drug cues. Any particular drug may have
different sites of action. Thus, drug cues may
produce both agonistic and antagonistic responses in
the same individual. Conditioned agonistic re-
sponses to drug cues may be important in relapse
because of their similarity with unconditioned drug
effects which serve to maintain drug taking behav-
iour by positive reinforcement (Stewart, deWit &
Eikelboom, (1984).
Solomon & Corbitt's (1974) opponent process
theory predicts that a drug engenders an O; or
agonistic process which leads to a ^ or antagonistic
process which serves to maintain homeostasis. It
provides a means of explaining the coexistence of
conditioned agonistic and antagonistic responses in
the same individual to the same environmental cues
at different times. Unlike Siegel's model, environ-
mental cues can come to elicit either a- (CSa) or b-
(CSb) processes. Solomon (1977) later speculated
that the direction of the CR would depend mainly
on the temporal relationship between the cue and
the a- or 6-process.
Donovan & Chaney (1985) have elaborated this
theory to account for differences in response
between dependent and non-dependent drinkers.
Essential to this is Opponent Process Theory's
predictions regarding the timing and strength of the
Zi-process. Solomon & Corbitt (1974) suggested that
with repeated administrations of the drug, the b-
process will beconie greater in magnitude and more
rapid in onset to a point where only a minimal
agonistic effect will be observed, followed rapidly
by a much larger and longer lasting antagonistic
effect. Donovan & Chaney (1985) propose that a
CSa will lead to a predominantly agonistic effect in
a relatively non-dependent drinker whereas in the
severely dependent drinker the same CSa will lead
to a predominantly antagonistic process.
Another theory which predicts relapse following
both agonistic and antagonistic responses to drug
cues, is that of Baker, Morse & Sherman (1987).
Drawing on the work of Wise & Bozarth (1982)
they postulate two distinct, mutually inhibitory
neural networks which are responsible for the
motivation of drug taking behaviour and hence,
relapse. Drug cues can activate both an appetitive
and a withdrawal relief network leading in either
case to relapse. In common with Donovan &
Chaney, they predict that in the more severely
dependent, drug cues will predominantly stimulate
the withdrawal relief network whereas in the less
dependent, the positive network will be more
important. A further prediction of this theory is that
the effects of cues will be affected by the position of
the drug taker in the cycle of intoxication and
withdrawal. In abstinent or withdrawing addicts
drug cues will activate the withdrawal relief net-
work.
So far we have emphasized the possibility of the
existence of both agonistic and antagonistic re-
sponses to environmental cues. In contrast to more
parsimonious models (e.g. Niaura et al, 1988), it
has been suggested that both types of response may
theoretically occur within the same individual either
simultaneously or at different times or in response
to different cues. The importance of this theoretical
prediction is that, as we shall see later, the direction
of the CR may be important in determining operant
responses. Further, the extinction of CRs to ARCs
in cue exposure treatment may have unpredictable
effects depending on the appetitive or aversive
nature of the CR and its relationship to the operant
response.
Craving and relapse
The concept of 'craving' has been important in the
development of cue exposure research. It has been
argued that the subjective experience of conditioned '
craving in response to drug cues is the important
determinant of relapse (Ludwig & Wikler, 1974).
We have considered craving separately from condi-
tioned responses because it represents an ambiguous
concept which serves to impede progress in the cue
exposure field. Ludwig, Wikler & Stark succinctly
described the status of craving in 1974, thus:
Although the related phenomena of 'craving' and
'loss of control' have been invoked as explana-
tions of relapse, there is little current agree-
ment . . . about their nature or even existance . . .
[It has been] argued that the construct of craving
represents a superfluous, logical tautology since it
is often defined by subsequent drinking behav-
iour.
As a remedy to this conceptual confusion Ludwig
& Wikler (1974) put forward the theory that craving
represented the 'cognitive symbolic correlate of con-
ditioned subclinical withdrawal' and that craving in
turn leads to alcohol-seeking behaviour and relapse.
This definition is also tautologous. This problem is
not helped by expanding the definition of craving to
include appetitive or drug-like subjective states.
Baker, Morse & Sherman (1987) have used the
term 'urges' to describe the subjective states associ-
ated with responses to drug cues. They suggested
that 'positive-effect urges' are associated with
appetitive cues whereas 'negative-effect urges' are
associated with aversive cues. They relate these
urges to the previously described underlying and
separate neural networks. While this theory is more
sophisticated than that of Ludwig & Wikler's view
of craving, it is also subject to the problem of
attributional bias. Attributional bias in an individu-
al's linguistic labelling of an internal physiological
state has been observed to exert a powerful effect in
other experimental settings (Schachter & Singer,
1962; Nisbett & Wilson, 1977). The subjective
experience described as a 'craving' or an 'urge' may
represent a variety of different internal states
between individuals and give rise to erronenous
interpretations of the effects of cue exposure. Also it
may be particularly difficult for an alcoholic in
treatment to say that he is craving (by definition,
thinking of relapse) if he has publicly committed
himself to abstinence.
Clearly, subjective responses cannot be ignored.
Further research is needed to elucidate the physio-
logical correlates of subjective states and in particu-
lar the effects of setting on attributions. Until this
has been done we argue that subjective responses to
ARCs should not be assumed to be indicative of any
particular underlying physiological state or behav-
ioural intention. It is possible in technical accounts
to describe subjective responses to ARCs in terms of
positive or negative affect (as suggested by Baker et
al., 1987), or indeed by using a variety of adjectives,
without recourse to the ambiguity of the concept of
craving.
Extinction of CRs to environmental cues
Several animal experiments have demonstrated that
CRs to drug cues can be extinguished by repeated
presentation of the CS without the unconditioned
stimulus of drug administration. Siegel et al. (1979)
demonstrated loss of tolerance to the lethal effect of
morphine and concluded that antagonistic responses
to morphine had been extinguished. Similar results
have been observed in respect of tolerance to the
analgesic effect of morphine (Siegal, Sherman &
Mitchell, 1980) and the hypothermic effect of
ethanol in rats (Mansfield & Cunningham, 1980).
These results suggest that, at least in animals, CRs
can be extinguished by unreinforced exposure to
drug cues.
Rankin et al. (1983) have proposed an alternative
model of the effects of repeated exposure to alcohol
cues in alcoholics. They draw a comparison between
alcoholism and phobic neurosis suggesting that
drinking alcohol in response to drug cues is similar
to phobic avoidance of a feared stimulus. While such
a comparison may be theoretically unwarranted they
proposed that unreinforced exposure to alcohol cues
would lead to extinction of a drinking response,
citing in support of this hypothesis the work of
Baum (1969). Baum, observed that rats who were
trained to escape from a shock by jumping onto a
ledge initially continued to try to escape when the
ledge was removed, but over repeated trials the
avoidance response extinguished.
Reiss (1980) has examined the implications of
expectancy theory of conditioning in the extinction
of phobic avoidance responses. Of particular poten-
tial relevance to cue exposure in drug and alcohol
dependence are the lessons drawn from Rescorla-
Wagner theory (1972) of Pavlovian conditioning.
During extinction of CRs, any new stimuli (e.g.
therapists) presented in compound with the target
stimuli (i.e. the ARCs), will gradually acquire
inhibitory properties (become safety signals in the
case of phobic subjects) as the excitatory properties
of the target stimulus declines. No further condi-
tioning will take place once the inhibitory properties
of the safety signal counterbalance the excitatory
properties of the feared stimulus. This will leave
some of the excitatory properties intact, 'protected'
by the existence of safety signals.
If we wish to extinguish CRs to ARCs the
Rescorla-Wagner theory suggests that maximum
extinction will be achieved when there are no
safety signals present. Thus therapist and other
novel stimuli should be minimal or gradually
phased-out in the therapeutic setting.
If, however, we assumed that in theory it is
possible to extinguish CRs to ARCs and that this
would decrease the probability of an operant
drinking response and hence relapse, what can we
expect to happen if an alcoholic then takes alcohol.
Conditioning theory would predict that the CRs to
ARCs would be reinstated in a much shorter time
than was required to acquire CRs previously.
While extinction of CRs to ARCs may in theory
be expected to reduce the likelihood of relapse in
alcoholics, assuming that such CRs are determinants
of relapse and that extinction leads to reduced rather
than increased operant drinking responses, vulnera-
bility to reinstatement of CRs following an initial
priming dose remains a problem. Further, several
experiments have shown that animals may experi-
ence spontaneous reinstatement following extinc-
tion which would further limit the potential effects
of cue exposure.
Finally, there is the problem of generalization. In
practise it would be impossible in a laboratory
setting to extinguish CRs to every ARC which a
drinker had been exposed to during an entire
drinking career: the animal experiments so far
described have had the advantage of establishing
CRs in a controlled setting and therefore the
experiments have the knowledge of which specific
drug cues to target in extinction. The most that
could be hoped for is that extinction of CRs to the
most salient stimuli (if they can be identified) might
generalize to other stimuli the natural drinking
environment. Alternatively, extinction could be
attempted in the natural environment, a suggestion
which was made by Blakey & Baker (1980) to which
we will return later.
The relationship between classical and operant
conditioning in relapse
Research in the cue exposure field has so far
assumed a simple relationship between CRs to
environmental stimuli and relapse, predicting a
decreased likelihood of relapse following extinction
of CRs. We now present evidence derived from
other areas of animal learning research which
suggests that there exists a more complex relation-
ship between classical and operant conditioning than
has so far been considered by cue exposure resear-
chers and which has important implications for cue
exposure treatment.
Classical and operant conditioning can be argued
to be different types of learning, the distinction
being more than just a procedural one. The focus of
classical conditioning research is the learning which
takes place as a result of an organism's experience
events which occur independently of its behaviour.
The focus of operant conditioning research is the
learning which takes place as a result of an
organism's experience of events which take place as
a consequence of its behaviour.
These two types of learning are clearly not always
separate: many situations occur in which both types
of learning may operate. The question is, what is the
nature of their relationship? We need to consider
what the results of this interaction could be for the
way in which drug or alcohol use is learnt and for
the way in which we might attempt to intervene in
those learnt behaviours.
A. Central emotional state theory. One theory of the
interaction between the two types of learning was
presented by Rescorla & Solomon (1967). They
suggested that central emotional states generated by
Pavlovian or operant reinforcers were important
determinants of the interaction between the condi-
tioning processes. The theory was elaborated be-
cause of the difficulties experienced by experimen-
ters demontrating the function of conditioned
responses as, for example, discriminative stimuli.
Williams (1965) found that lever pressing for food
preceded salivation. If the salivatory response had
served a discriminatory function it should have
occurred before the lever pressing.
The value of reinforcement in either the Pavlo-
vian or operant paradigm can be characterized as
aversive or appetitive. Organisms can learn about
what predicts the occurrence or absence of either
type of event/reinforcer. It has been proposed that
if the value of the UCS in the Pavlovian paradigm or
the reinforcer in the operant paradigm are the same,
then they become mutually facilitative. If they are
opposite in value, for example if one were appetitive
and the other aversive, then the operant and
classically conditioned responses become mutually
inhibitory. An example of this has been described by
Rescorla & Lolordo (1965) who found that dogs
trained to avoid a shock by pressing a bar would
increase their reponding (operant) if they heard a
tone that had previously been paired with shock
(classical). Since shock is aversive, any stimuli
associated with it arouse an aversive central emo-
tional state. So if dogs are bar pressing motivated by
the central emotional state of fear, a tone signalling
shock will increase their central emotional state,
thereby increasing their rate of operant responding.
Conversely, if the dogs were bar pressing to avoid
shock and heard a tone which had previously been
associated with food, a positive central emotional
state, bar pressing decreases because the positive
central emotional state inhibits the negative central
emotional state.
Many of the predictions made by Rescorla &
Solomon have been tested experimentally. Needless
to say there have been failures to confirm the
predictions as well as successes. For example,
Lolordo (1971) found a signal for food produced
increased responding for food, a success, whereas
Azrin & Hake (1969) found the opposite, a failure.
Nevertheless, the implications of these findings for
extinction of CRs to ARCs in cue exposure are
interesting. In the typical cue exposure treatment
setting, ARCs are repeatedly presented without
ingestion of alcohol. Let us suppose that conditioned
antagonistic responses (CAntRs) occur, and that as
these CRs are opposite in direction to the usual drug
effects and are aversive in nature. These CRs should
be extinguished as the UCS, alcohol, signalled by the
CSs (i.e. the ARCs) does not occur. We could
suppose that the central emotional state associated
with the reinforcement, drinking, is negative since
the CAntRs are aversive, and that drinking is an
avoidant response. But also suppose that the act of
drinking as an operant response to ARCs is associated
through learning history from the beginning of
drinking with a positive central emotional state
(drinking, not to relieve withdrawal, but for a
positive, hedonic drug effect). If the CAntRs to
ARCs are extinguished, the concommitant negative
central emotional state is reduced. But according to
two process theory this negative central emotional
state may have been opposing the positive central
emotional state motivating operant drinking. So the
positive central emotional state now producing the
operant response will be disinhibited, making the
strength/probability of operant responding more
likely. Drinking will not necessarily decrease at all
even though CRs have been extinguished.
B. Expectancy theory. Another theorization of the
interaction between different kinds of learning can
be found in expectancy theory, as outlined by BoUes
(1972). The general implication of expectancy
theory is that by a form of practical inference an
organism will decide upon appropriate behaviours
based on its representation of action to consequence
in the operant paradigm. This theory does not differ
from conditioning theory in terms of its predictions
in many areas. One differential prediction, however,
concerns the appetitive case, which may be of
particular interest in looking at conditioned learning
in drinking behaviour. Whereas central emotional
state theory predicts that an appetitive instrumental
paradigm will produce increased responding when a
CS signals appetitive reinforcement, because the two
central emotional states are additive, expectancy
theory predicts a decrease. Conversely, a decrease in
positively reinforced responding when the CS is
aversive is predicted by two-factor theory because
the two central emotional states are opposite in value,
whilst expectancy theory predicts the opposite. The
reasoning for this in expectancy theory is that since
an appetitive CS indicates that reinforcement is
going to occur, the organism does not see the need to
make an operant response for reinforcement that it
believes is going to occur anyway and will decrease
responding. Conversely, where the CS predicts an
absence of a desirable event the responding for
positive reinforcement will increase because the
organism calculates that more work is required to
produce the reinforcer for which the CS predicts
non-occurrence.
But this may not be the end of the story either.
Mackintosh (1983) has argued that theories con-
cerning classical and operant interactions must also
take account of peripheral response competition in
the two types of associative learning. For example,
Lolordo, McMillan & Riley (1974) in an experi-
ment with pigeons, found that the interactions
between Pavlovian and operant schedules could be
influenced by arranging the experiment so that
Cue exposure treatment in alcohol dependence Ti\
peripheral CRs competed with, or facilitated the
operant response (for a review see Schwartz &
Gamzu, 1974).
Clearly, the relationship between classical and
operant conditioning is complex. We do not have a
theory which adequately explains and predicts the
outcomes of interactions between classical and
operant conditioning. In addition we do not have a
clear idea of the kinds of operant and Pavlovian
contingencies involved in drug taking. Therefore we
should not assume that extinguishing CRs to drug
cues will have the desired effect on the variable of
central interest, drug taking.
Cognitive models of relapse
The concept of expectancy has been applied to
explain the process of relapse. BoUes (1972) sug-
gested that expectancy has both informational and
incentive components which will influence future
behaviour. A drinker will have a belief about the
effects of alcohol (e.g. relaxation) and attach a value
to the desirability of such an effect (Marlatt,
1985a). Thus a positive outcome expectancy de-
scribes a desirable and rewarding outcome and a
negative outcome expectancy describes an undesira-
ble or aversive outcome. Marlatt suggests that in a
given situation a drinker will take alcohol if a
positive outcome expectancy is attached to drinking.
A further elaboration of this model is that craving
is synonymous with positive outcome expectancies
which can be elicited by drug cues through classical
conditioning (Marlatt, 1985a, p. 140). Marlatt,
however, suggests that conditioned learning rarely
precipitates relapse in comparison to, amongst other
factors, positive and negative mood states or social
pressure to drink (Marlatt, 1978; Chaney, O'Leary
& Marlatt, 1978). Attributional processes, however,
influence a subject's view of causal mechanisms in
relapse (Schachter & Singer, 1962). Thus, in a
situation where social pressure is exerted on an
individual to drink it is possible that alcohol related
cues are also present (e.g. the sight and smell of
alcohol) but that relapse is attributed to social
pressure rather than CRs (Heather & Stallard,
1989). Indeed social pressure in itself could act as a
discriminative stimulus in an operant drinking
response. Mood states may operate in a similar way.
Alternatively, a negative mood st^te could bring
about relapse through its similarity with a condi-
tioned antagonistic response by a process of general-
ization. Recent work has suggested that mood states
can elicit conditioned withdrawal (Childress et al,
1987; Litt et al, 1988).
Bandura's (1977, 1981, 1982) theory of self-
efficacy may provide an important additional di-
mension to our understanding of the effects of cue
exposure on relapse. He suggests that
"In the face of difficulties people who entertain
serious doubts about their capacities slacken their
efforts or give up altogether, whereas those who
have a strong sense of efficacy exert greater effort
to master the challenges" (Bandura, 1981, p. 201).
Self-efficacy is believed to interact with outcome
expectancy in such a way that an alcoholic faced
with the possibility of consuming alcohol will drink
in the combined presence of high positive outcome
expectancies and low perceived self-efficacy. The
effect of cue exposure may be to increase positive
outcome expectancies as we have suggested and
relapse would occur if this is combined with low
self-efficacy. Bandura also predicted that increased
aversive arousal, in particular that over which one
had no control, would lead to decreased self-efficacy
(Bandura, 1981). Thus arousal induced by CRs to
ARCs may have a direct effect on self-efficacy as
well as outcome expectancy. This view is supported
by a recent experimental study of cue exposure in
alcoholics (Cooney et al., 1987).
It is also possible that the experience of a high
level of arousal in the cue exposure setting which is
not followed by consumption of alcohol may lead to
increased self-efficacy. In effect, an individual may
form an internal attribution of mastery over his
environment and urges to drink alcohol. The
implication for cue exposure as a treatment is that
subjects should be encouraged to regard their
participation as involving the active implementation
of effective coping responses. The phasing out of
safety signals, such as the presence of a therapist,
during cue exposure treatment may also increase the
likelihood of the formation of such an internal
attribution.
That self-efficacy may be an important factor in
relapse is suggested by the work of Condiotte &
Lichtenstein (1981) who found that ex-smokers
who relapsed following treatment tended to have
low self-efficacy compared to non-relapsers. Di
Clemente (1981) reported a similar finding. There
is strong empirical evidence of the power of self-
efficacy judgements in predicting drinking behav-
iour (Rist & Watzl, 1983; Annis & Davis, in press).
It has also been suggested that skill training to
increase self-efficacy may be useful in preventing
alcoholic relapse (Chaney, O'Leary & Marlatt,
1978; Annis & Davis, in press). However, that self-
efficacy judgements may be self-fulfilling prophe-
sies and act as a method of dissonance reduction,
rather than representing a causal mechanism, re-
mains to be determined.
Nevertheless, we concur with the views of Niaura
et al. (1988) and Marlatt (1988) that the question as
to whether cue exposure treatment may prevent
relapse not only by extinction of conditioned
responses but also by change in outcome expectancy
and self-efficacy deserves further consideration.
Self-efficacy theory is not incompatible with condi-
tioning theories of relapse, but instead offers a
different level of description and explanation.
Conclusions regarding the competing theoretical
models of relapse
We have described the development of conditioning
theories of relapse since Wikler's original formula-
tion (1965). There seems to be little doubt that CRs
to drug cues develop following repeated administra-
tion of drugs in animals and that it is possible to
extinguish these responses during unreinforced cue
exposure. The terms 'conditioned agonistic' and
'antagonistic response' (CAgR, ContR) afford
greater conceptual clarity than 'conditioned with-
drawal'. If, as has been suggested, both types of
response can occur within the same individual either
simultaneously or at different times or in response to
different cues, and that the interaction between
Pavlovian and operant contingencies is more com-
plex than has so far been assumed, the effects of
extinction during cue exposure may be highly
unpredictable. We recommend a more detailed
investigation of the effect of the directionality of CRs
on operant drinking responses and the effects of
extinction.
Assuming that extinction of CRs leads to reduced
drinking behaviour, however, the effects of cue
exposure as a treatment will theoretically be limited
by the problem of reinstatement. The best one
might therefore expect from cue exposure treatment
is an increased latency to relapse rather than a
reduction in the extent of a relapse. In addition, the
problems of safety signals and generalization leads
one to the conclusion that cue exposure in the
natural drinking environment, with minimal thera-
pist presence, might be more likely to influence
drinking behaviour than exposure conducted in a
laboratory jetting; a^view which has been previously
expressed, but not so far adequately investigated.
Because of the ambiguity of the term 'craving'
and the effect of attributions we have suggested that
subjective responses to ARCs should not be as-
sumed to reflect any particular underlying physio-
logical response or behavioural intention. Subjective
states can be described in technical studies in terms
of a variety of adjectives without recourse to the
concept of craving. This should go a long way
towards resolving conceptual confusion in the field.
Social learning theorists such as Marlatt (1985a)
have de-emphasized the importance of CRs to
ARCs in explaining relapse, by applying an overly
narrow definition of conditioned stimuli and rein-
forcers (Heather & Stallard, 1989). This has led to a
dichotomy in relapse research between conditioning
and social learning theories, with a resultant lack of
cross-fertilization of ideas. The possibility that the
effects of cue exposure treatment may be mediated
either instead or in addition by alterations in
outcome expectancies or self-efficacy deserves fur-
ther consideration. It is possible that cue exposure
shares a common effect with a more 'office based'
skills training or relapse prevention approach, and
that rather than simply extinguishing CRs, the
alcoholic undergoing cue exposure treatment may
acquire coping strategies to avoid future drinking.
We would argue that self-efficacy and conditioning
theories of relapse are complementary rather than
contradictory, differing in terms of their level of
description and explanation.
Laboratory studies or conditioned responses to
alcohol related cues in human alcohol depen-
dence
So far we have reviewed the theoretical develop-
ments in the study of CRs to environmental cues
since Wikler's (1965) original formulation. From
the animal literature, there is considerable evidence
in support of the existence of both conditioned
agonistic (CAgR) and antagonistic (CAntR) re-
sponses which may be modified by extinction. In
reviewing laboratory studies which have examined
CRs to ARCs in human alcohol dependence there
are three main questions which need to be ad-
dressed. What is the relationship between CRs to
ARCs and alcohol dependence? What is the nature
of these responses? Is there any evidence to
implicate such responses in relapse? Although some
of these issues have previously been explored by
Niaura et al. (1988), we offer here an alternative
interpretation of the evidence.
Comparison of studies in this area is complicated
by the different aims of investigators and the variety
of methodologies employed. In broad terms this
work can be divided into five categories:
(1) Studies of cued responses in alcohol depen-
dent and social drinkers.
(2) Studies comparing responsivity to alcohol-
related and neutral stimuli.
(3) Studies of the influence of expectancy on
CRs.
(4) Studies of the development of CRs to ARCs
in social drinkers.
(5) Priming dose studies.
While several investigators have employed a
combination of these methodologies, studies of cued
responses have a broadly similar design. The subject
is presented with alcohol related stimuli which often
include the sight and smell of alcohol. This has been
described as cue exposure. With the exception of
priming dose studies, alcohol is not consumed.
Physiological and subjective measurements are
taken before and after cue presentation. The
difference between these measurements is deemed
to be a response.
CRs to ARCs in alcohol-dependent and social
drinkers
An important problem in the interpretation of these
studies is that few investigators have specified the
degree of alcohol dependence of their subjects.
Newlin (1985a) has found antagonistic responses to
alcohol cues in social drinkers given an non-
alcoholic drink which they were led to believe
contained alcohol. He has also found enhanced
antagonistic responses to placebo in sons of alcohol-
ics suggesting the possibility of a genetic predisposi-
tion to cued responses (Newlin, 1985b).
Several studies have observed differences be-
tween severely dependent and moderately or non-
dependent subjects (Stockwell et al., 1982; Rankin
et al, 1982; Kaplan et al, 1983; Laberg, 1986; Corty
et al, 1988). Although these findings are consistent
with conditioning theory predictions, it is possible
that conditioned responses to alcohol cues may
develop after only a few exposures. It is perhaps not
surprising therefore that several authors have failed
to find consistent differences between alcohol de-
pendent and social drinkers. Bearing in mind that
the limitations inherent in the term 'alcoholic', it
will be used in future sections as a form of
shorthand for a subject who has presented to a
clinical service with alcohol-related problems and an
unspecified degree of alcohol dependence since
greater descriptive precision is not possible from the
majority of studies under review.
A further problem in determining the specificity
of conditioned responses to alcohol cues in alcohol-
ics is indicated by a number of studies comparing
the psychophysiology of alcoholics and controls.
Coopersmith (1964) for example found that alco-
holics were more responsive than controls in terms
of skin conductance. This finding was replicated by
Chandler et al. (1975) during a demanding neuro-
psychological task. They also found greater heart
rate variability in alcoholics in spite of finding no
difference on these measures during a resting
period. In contrast to this Chotlos and Goldstein
(1967) reported that alcoholics' heart rate increased
and skin conductance decreased during silent peri-
ods of the experiment.
These comments notwithstanding, several studies
have found differences between alcoholics and
controls. Increased subjective desire for alcohol,
skin conductance level and heart rate have been
observed to differentiate alcoholics from controls
following CE (Kaplan et al, 1983; Kaplan et al,
1985; Laberg, 1986). A greater number of studies
have found no differences on these measures
(Pomerleau et al, 1983; Dolinsky et al, 1987; Monti
et al, 1987; Corty et al, 1988).
The predominant explanation for these changes in
HR and SCL in response to ARCs is that of an
increase in physiological arousal (Kaplan et al,
1985; Laberg, 1986). This view of arousal (Malmo,
1959) has been the subject of considerable criticism.
For example Lacey (1959) has described the
concept of autonomic response specificy suggesting
that HR and SCL can increase or decrease depend-
ing on the nature of the stimulus. Lacey later
concluded (1967) that physiological responses
should be viewed in the context of interactive
feedback systems which bear a complex relationship
to emotion. Similarly, in reviewing studies to tonic
HR responses to stimuli Elliot (1974) observed
"There are in these data, in short, grounds for
scepticism of any view of the motivational
significance of HR" (p. 536).
Such observed responses are also inconsistent
with a model of CAntRs to ARCs (described above)
since alcohol has been consistently shown to have
the unconditioned effects of tachycaria (Docter &
Perkins, 1960; Docter et al, 1966; Holmberg &
Martens, 1955; Mendelson & LaDou, 1984) and
increased skin conductance (Carpenter, 1957;
Greenberg & Carpenter; 1957; Levenson et al.,
1980).
Two studies have found a peripheral hypothermic
response to CE (Laberg, 1986; Dolinsky, 1987) and
two have found no measurable change (Kaplan et
al, 1983; Corty et al., 1988), although the latter
study found that temperature was affected by the
order of presentation of neutral and alcoholic
stimuli in alcoholics. Again this would appear
antithetic to a CAntR model where conditioned
hyperthermia is predicted (Crowell et al., 1981; Le
et al., 1979; Mansfield & Cunningham, 1980). That
is, unless one considers the interactive nature of
physiological response systems (Lacey, 1967). Alco-
hol not only has the unconditioned effect of
decreasing temperature, it also produces vasodila-
tion (Docter & Bernal, 1964; Ritchie, 1965; Roth &
Sheard, 1947). Thus an antagonistic vaso constric-
tive response, which has been observed in social
drinkers in response to CE (Newlin, 1985a), could
account for this peripheral hypothermic response.
Salivation in response to CE has been measured
directly by measuring weight gain in dental rolls or
indirectly by measuring digastricus muscle electro-
myographic activity, and has been reported to
differentiate alcoholics from controls (Pomerleau et
al., 1983). Subsequent studies have failed to repli-
cate this finding (Kaplan et al., 1985; Monti et ah,
1987; Corty et al, 1988), although two of these
studies found that salivation in alcoholics was
influenced by the order of stimulus presentation
terms of both an increase (Monti et al, 1987) and a
decrease (Corty et al, 1988) in salivation when
alcohol presentation followed a neutral stimulus.
Pomerleau et al. (1983) have explained their
observations in terms of both appetitive arousal and
conditioned responding to alcohol stimuli. Beazell &
Ivy (1940) noted a fall in salivation following
alcohol consumption and Kissin et al. (1959)
observed a decrease in salivia sodium, interpreting
the change as due to parasympatholytic effects of
alcohol. Pomerleau et al's findings may indicate the
existence of a salivatory CAntR to ARCs. Until
these findings have been replicated however, the
specificity of such a response remains uncertain.
Other responses to ARCs which have been
reported include raised serum insulin and glucose
and decreased cortisol (Dolinsky et al, 1987) the
significance of which is at present unclear. One early
study found pupillary dilation in response to the
smell of a favourite alcoholic drink in alcoholics
(Kennedy, 1971). In support of the social learning
model of relapse, cue exposure has been found to
increase positive and decreased negative outcome
expectancies of alcohol's effect (Cooney etal, 1984;
Laberg, 1986; Cooney et al, 1987; Stockwell et al,
1982). In this context Cooney et al (1987) also
noted that alcoholics reported decreased self-effi-
cacy, and desire for alcohol was found to be
inversely correlated with confidence in being able to
resist alcohol.
Alcohol-related versus neutral stimuli
That cued responses are specific to alcohol and not
merely the experimental setting has been demon-
strated by several studies comparing the effects of
alcohol-related and neutral stimuli in alcoholics
(Pomerleau et al, 1983; Kaplan et al, 1983; Eriksen
& Gotestam, 1984; Kaplan et al, 1985; Laberg,
1986; Cooney et al, 1987; Monti et al, 1987). As
suggested earlier these experiments are subject to
methodological difficulties which serve to affect the
possibility of observing a difference between condi-
tions. The order of presentation of the stimuli,
expectancy of receiving alcohol and the possibility
of a carry over effect from one stimulus to another
may all serve to reduce the likelihood of finding an
observed difference between responses to alcoholic
and neutral stimuli. It adds greater weight to these
positive findings therefore that differences between
alcoholic and neutral stimuli have been observed in
terms of increased desire for alcohol, SCL, HR,
salivation and decreased peripheral skin tempera-
ture.
Expectancy and CRs to ARCs
The third group of studies are those which involve
manipulation of instructional set or expectancy
through a full or partial realization of the balanced
placebo design (Marlatt & Rosenhow, 1980, 1981).
Priming dose studies have also made use of this
experimental manipulation to which reference will
be made in a later section.
The prediction of this experimental design is that
responses to alcohol cues will be dependent on the
belief concerning the alcohol content of a stimulus
rather than its actual content. Several studies have
demonstrated the importance of this effect in CE.
Kaplan et al (1983) found that alcoholics who were
told that a drink contained alcohol responded with
increased desire for alcohol compared to controls.
This finding has been replicated in several similar
studies (Kaplan et al, 1984; 1985; Laberg, 1986)
both in terms of subjective and physiological
responses (see also priming dose studies). These
results are in keeping with a conditioning model in
that a positive expectancy of receiving alcohol can
be seen as 'part of the CS (complex) associated with
past alcohol consumption' (Shapiro & Nathan,
1986). Further, Newlin (1985a) has demonstrated
in social drinkers that CAntRs only occur in those
subjects who consume a placebo drink which they
believe to be alcohol. Staiger & White (1988) on the
other hand have de-emphasized the importance of
expectancy in conditioned responses to alcohol cues
by demonstrating that a conditioned heart rate
response occurred irrespective of subject's expec-
tancy. This contradicts the proposal made by
Newlin (1986) and Shapiro & Nathan (1986) that
expectancy acts as a determinant of the conditioned
compensatory response. The expectancy hypothesis
should not be rejected on the basis of this one study.
On balance, expectancy should be seen as an
important determinant of a CR.
Experimental induction of CRs to ARCs in social
drinkers
Several investigators have sought to establish CRs
to novel stimuli associated with alcohol consump-
tion in social drinkers. This approach is theoretically
preferable to post hoc explanations of responses to
alcohol cues in established alcoholics and avoids the
complicating factor of differences in pre-existent
physiological responsivity between alcoholics and
non-alcoholics referred to above.
Dafters & Anderson (1982) observed the devel-
opment of tolerance to the tachycardia effect of
ethanol in normal social drinkers following repeated
alcohol exposure in a novel and distinctive environ-
ment. While they did not attempt to demonstrate an
antagonistic response to placebo, they concluded
that a conditioned heart rate response to environ-
mental stimuli served to counteract the uncondi-
tioned alcohol effects.
Later, Newlin (1984) gave social drinkers alcohol
in a novel environment on four occasions. Subjects
then given a placebo drink believed to be alcohol
showed a decrease in pulse transit time and finger
temperature in comparison to controls. In a similar
study, involving 10 exposures to alcohol in a
distinctive and novel environment, Shapiro & Na-
than (1986) found evidence of tolerance to alcohol
on a cognitive vigilance task in same treated subjects
compared to controls, but found no effect of placebo
on heart rate, finger pulse volume or peripheral
temperature.
More recently Staiger & White (1988) have
reported antagonistic heart rate and temperature
responses to alcohol cues following conditioning in
two distinctive environments, each for four sessions.
They also found that cues associated with the room
tended to produce a CAntR whereas cues associated
with the drink tended to produce a CAgR, demon-
strating both drug-like and drug-opposite responses
within the same response systems.
Priming dose studies
Priming dose studies differ from studies of cue
exposure so far described in that alcohol is actually
consumed. Subjects are generally then presented
with further alcohol and instructed to resist the
desire to drink or are given operant tasks to
perform. While these studies provide an interesting
insight into operant responses in alcoholics, analysis
of psychophysiological responses to presentation of
alcohol cues after consumption is complicated by
the unconditioned effects of alcohol. This problem
is particularly salient if a CAntR to ARCs is
predicted: the UCR effectively counteracting any
CR effects. Some studies have examined responses
both befoi-e and after consumption of a priming dose
(Kaplan et al., 1983; 1984; Laberg, 1986). Priming
dose studies were conducted early in the history of
cue exposure and provided an impetus for research
into cue exposure as a treatment method.
An increase in desire for alcohol in alcoholics
receiving priming doses of alcohol has been consis-
tently observed (Engle & Williams, 1972; Ludwig et
al., 1974; Hodgson et al., 1979; Rankin et al, 1979;
Stockwell et al, 1982; Kaplan et al, 1983; Kaplan et
al, 1984; Laberg, 1986; Laberg & Ellertsen, 1987),
particularly when the subjects believed that they had
consumed alcohol (Ludwig et al, 1974, Stockwell et
al, 1982; Kaplan et al, 1983; Kaplan et al, 1985;
Laberg, 1986).
Although interpretation of physiological re-
sponses to cue exposure following a priming dose of
alcohol is complicated as described above, results
seem to be generally consistent with those of non-
priming CE studies with increases in SCL (Ludwig
et al, 1974; Kaplan et al, 1984; Laberg, 1986;
Laberg & Ellertsen, 1987) and HR (Ludwig et al,
1974; Hodgson et al, 1979; Stockwell et al, 1982;
Laberg & Ellertsen, 1987). Other observed physio-
logical changes following priming dose CE include
increased tremor amplitude (Ludwig et al, 1974)
and acceleration (Rankin et al, 1979; Stockwell et
al, 1982), decreased temperature (Rankin et al.
1979; Laberg, 1986), increased alpha wave EEG
activity and respiratory rate (Ludwig et al, 1974).
Several investigators employing a priming dose
paradigm have been interested in the effects of an
initial dose of alcohol on subsequent drinking
behaviour in the experimental setting. In Engle &
Williams' (1972) study, for example, subjects were
instructed that alcohol was obtainable in another
part of the hospital and were given detailed
instructions on how to obtain it. Only one subject,
however, asked for further alcohol, interestingly a
subject who had been told that he had been given
alcohol but in fact had received placebo. In an
operant task on the other hand, Ludwig et al. (1974)
found that subjects who were told that they had
received alcohol worked more for a further drink as
did those subjects who actually received a large
priming dose of alcohol compared to controls.
Similarly, Hodgson et al. (1979) found that alcohol-
ics given a large priming dose showed increased
speed of drinking a further drink in comparison to
controls. The same group later replicated these
findings (Rankin et al., 1979; Stockwell et al,
1982). Marlatt, Demming & Reid (1973) have also
demonstrated that both alcoholics and social drink-
ers drank significantly more beverage when they
believed they were drinking vodka. Conversely,
subjects told they were drinking tonic consumed
significantly less beverage even when the drink
contained vodka.
Other studies have not found changes in operant
responses following a priming dose of alcohol in a
variety of experimental designs (Kaplan et al, 1983;
Laberg, 1986). Exposure to alcohol cues in the
absence of consumption of a priming dose has not
been found to infiuence alcoholics' drinking behav-
iour in a laboratory setting (Griffiths et al, 1976;
Pomerleau et al, 1983; Monti et al, 1987).
Conclusions regarding the evidence for conditioned
responses to ARCs in humans
There are clearly many methodological problems
involved in determining the nature of CRs to ARCs,
not least the problem of response specificity. That
social drinkers might exhibit CRs to ARCs under-
lines the importance of defining subjects drinking
history and degree of dependence in cue exposure
studies.
To return to our original questions regarding
laboratory studies of CRs to ARCs, first, the
evidence suggests that while CRs may develop early
in an individual's drinking career increased respond-
ing is associated with higher degrees of alcohol
dependence. This could find application in the
clinical assessment of alcohol dependence. Further,
that CRs are specific to ARCs and not merely an
artifact of the experimental setting has been demon-
strated in several studies comparing alcohol-related
and neutral stimuli. That differential responding to
alcohol-related and neutral stimuli has been ob-
served in spite of several factors which reduce the
likelihood of this occurrence, adds greater weight to
the specificity of ARCs.
In terms of the nature of CRs to ARCs, simplistic
concepts such as arousal, appetitive responding and
craving are inadequate in explaining the complexity
of the observed responses. Heart rate, skin conduc-
tance and temperature responses are consistent with
a CAgR, whereas finger pulse volume and salivatory
responses are consistent with a CAntR. Further-
more, both types of physiological response have
been observed to occur within individual response
systems to different ARCs. Individual physiological
measures, however cannot be viewed in isolation of
each other. Thus there should be greater concentra-
tion on the multivariate patterning of CRs to ARCs.
Recent advances in other areas of psychophysio-
logical research, in particular a systems approach
(Schwartz, 1982) has much to offer in this respect.
For example, it is unclear at present whether an
observed hypothermic response is a primary (cen-
trally mediated) CAgR to ARCs or a secondary
(peripherally mediated) response to a primary
vasoconstrictive CAntR. The monitoring of a
greater number of physiological parameters as well
as the use of multivariate statistical techniques will
contribute greatly to our understanding of these
interactions.
Another point of interest in relation to the nature
of CRs to ARCs is the finding that priming and non-
priming dose studies yield similar physiological
results in spite of the probable co-occurrence of
tJCRs in the former. Certainly, skin conductance,
heart rate and temperature responses may be
isodirectional (CAgR) to a UCR, leading to similar
findings in the two paradigms. Alternatively, this
may be a refiection of the existence of cognitive
dissonance in alcoholic compared to social drinkers
in both experimental paradigms. We know that
following exposure to ARCs, both alcoholics and
controls report increased desire for alcohol and have
a positive outcome expectancy of the effects of
alcohol. In comparison to controls, however, alco-
holics may experience cognitive dissonance in that
they have also committed themselves to an absti-
nence goal (Lipscomb & Nathan, 1980). Festinger
(1957) has described cognitive dissonance as an
unpleasant subjective experience. As a method of
dissonance reduction, an alcoholic may form an
external attribution that he is 'craving', which may
be seen as a phenomenon over which one has no
control. Dissonance has been observed in other
experimental paradigms to lead to sympathetic
activation with the effects of vasoconstriction (Ger-
ard, 1967), increased skin conductance level
(Quanty & Becker, 1974) and tachycardia (Caci-
oppo & Petty, 1982). Vasoconstriction could as we
have suggested account for peripheral hypothermia.
While this formulation of the effect of ARCs in
alcoholics is speculative, the role of cognitive
dissonance in CRs to ARCs deserves further in-
quiry.
Experiments investigating the effects of manipu-
lating expectancy suggest that expectancy of receiv-
ing alcohol is an important determinant of CRs to
ARCs. Future research should ensure that this
factor is taken into account in experimental design.
Finally, the evidence linking CRs to ARCs and
relapse is currently lacking. The fact that no
published study has found a link between CRs to
ARCs and relapse has important ramifications for
the potential of cue exposure as a treatment
approach. A comprehensive prospective study of
CRs to ARCs and relapse is much needed. The
induction and extinction of CRs in social drinkers
has particular appeal as an experimental paradigm in
that conditioning history in a novel environment can
be more carefully controlled than with clinical
populations of alcoholics presenting for treatment.
A better understanding of the relationship between
CRs and operant drinking responses in this setting
could provide a model for relapse in alcoholics.
Cue exposure as treatment
That exposure to alcohol related cues, combined
with prevention of a drinking response, might
infiuence drinking behaviour was suggested several
years before any systematic research into the nature
of responses to cues, or their effect on operant
responses had been conducted. Nevertheless these
early optimistic studies, mostly single case designs
(e.g. Pickens et al., 1973; Hodgson & Rankin, 1976,
1982), gave considerable impetus to research into
the application of CE as a potential treatment for
addictive disorders.
Using an individualized treatment approach com-
bined with coping skills training Blakey & Baker
(1980) exposed six alcoholic subjects to their
favourite drink in a variety of settings. This
included some subjects who were exposed to alcohol
cues in a laboratory setting and some who received
exposure in a more typical drinking environment.
While the exposure design was not standardized and
was combined with other treatments the authors
found that 4 out of 6 subjects were abstinent at
between 2 and 12 months follow-up. They con-
cluded that the treatment approach held some
promise and warranted fuller investigation.
The first controlled trial of cue exposure was
conducted by Rankin, Hodgson & Stockwell (1983).
Based on a theoretical model of treatment for
compulsive behaviours (Rachman & Hodgson,
1980) five severely dependent alcoholics, who were
hospitalized and had been abstinent for 7-10 days,
were given a priming dose of alcohol and were then
asked to resist drinking further available alcohol (in
vivo CE). Exposure involved holding and smelling a
glass of their favourite drink for 3 min on 18
occasions spread over 8 days. A control group of five
alcoholics were asked to imagine being exposed to
alcohol during the same period (imaginal CE).
Compared to the control group the in vivo CE
group showed a decrease in desire for alcohol and
difficulty in resisting a drink across sessions. It was
also found that the time taken to consume a dose of
alcohol during a subsequent behaviour test had
significantly increased in the in vivo group com-
pared to controls. The authors regarded speed of
drinking as a behavioural measure of craving and an
analogue of drinking in the natural environment. A
follow-up study would be helpful in establishing
whether these changes observed in the laboratory
extended to drinking behaviour in the natural
environment.
Further, the physiological measures of HR and
tremor, while increased during CE, did not show a
decrement across sessions and did not differentiate
in vivo CE subjects from controls (Rankin, 1981).
The authors prediction of changes in physiological
response to CE following treatment was not con-
firmed by the results although may have been
affected by measurement error or the confounding
effect of the subjects unconditioned response to the
priming dose of alcohol.
A more recent study by Laberg & EUertsen
(1987) employed a broadly similar design, but
included additional control groups. A total of 16
severely dependent alcoholics were assigned to four
groups each containing 4 subjects. One group was
equivalent to Rankin et al.'s (1983) in vivo CE
group in that they received a priming dose of alcohol
and were asked to resist further available alcohol
( P + / C+ ) . A second group received an alcoholic
priming dose, but were exposed to a soft drink
( P+/ C) . The other two groups received no
priming dose followed by exposure to either a soft
drink CE ( P - / C - ) or alcohol ( P - / C + ). While
the groups were too small to form any firm
conclusions, the groups receiving a priming dose of
alcohol showed greater initial increases in desire for
alcohol, difficulty resisting alcoliol, skin conduc-
tance level, non-specific skin conductance responses
and heart rate during cue exposure. These changes
tended to decrease both within and across sessions
regardless of group although the greatest decreases
occurred in subjects who had been given an
alcoholic priming dose (P + ).
The authors concluded that CE is 'an effective
treatment method for severely dependent alcohol-
ics'. Closer analysis of the study however reveals
that in addition to the absence of follow-up data to
support this view, and the fact that responses to
alcohol cues were not compared with that of neutral
stimuli in a within subject cross over design, it is not
clear whether the subjects simply showed
habituation to the experimental setting over time.
Further, as in the previous study, it is unclear to
what extent these laboratory findings might be
applicable to the natural setting. Other investigators
have drawn attention to the limitations of the
demand characteristics of a controlled laboratory
setting on alcoholic's drinking behaviour (Lawson et
al., 1976).
Cue exposure has also received attention as a
potential treatment for heroin and cocaine addiction
(Childress et al., 1986a; Legarda, 1989; Bradley &
Moorey, 1988). In a variety of studies Childress and
co-workers (Childress et al., 1984, 1986a, 1986b,
1986c) have consistently demonstrated subjective
and physiological responses to drug related stimuli
compared to neutral stimuli in both abstinent and
methadone maintained heroin addicts. Increases in
desire for heroin, skin conductance level and
respiratory rate and decreases in skin temperature
have been reported.
While repeated unreinforced exposure to a
variety of drug related stimuli has resulted in
significant decreases in subjective desire for drugs,
attempts to extinguish physiological responses have
been unsuccessful (Childress etal, 1986d). Legarda
(1989) recently reported broadly similar results. It
is possible that this failure to extinguish physiolog-
ical responsiveness has contributed to the lack of a
significant influence of the treatment on outcome.
McLellan et al. (1986) found that 35 sessions of
exposure to drug-related stimuli combined with
cognitive behavioural therapy conferred no advan-
tage over cognitive behavioural therapy alone in a
group of methadone maintained heroin addicts at 6-
month follow-up. Both treatments conferred a
marginal advantage over drug counselling.
Further study is required to examine the influ-
ence of duration of exposure and stimulus salience
on extinction of physiological responses in heroin
addicts. Some commentators have suggested that
these factors may have a critical effect on extinction
(Legarda, 1989; Bradley & Moorey, 1988). Further,
no follow-up study comparable to that of McLellan
et al. (1986) has so far been conducted in the alcohol
dependence field.
Conclusions
In summarizing over 20 years of research and a large
number of studies, it is necessary to come to the
disappointing conclusion that no published human
study has so far demonstrated that CRs to environ-
mental cues represent a causal factor in relapse in
either drug or alcohol dependence. Further, no
treatment study has demonstrated that cue exposure
has any advantage over more conventional and less
intensive interventions in terms of relapse. We must
therefore be cautious not to allow fashions to dictate
treatment trends until an adecjuate demonstration
has been made that cue exposure is effective.
It would be contrary to the evidence however, to
suggest that cue exposure has not progressed since
Wikler's innovative theory was proposed. Several
findings provide an essential base of knowledge
from which future research may proceed. Several
studies employing a variety of research designs have
found CRs to both drug and alcohol related cues
which develop early in a drug using career, the
magnitude of which is related to degree of depen-
dence. CRs may be both agonistic and antagonistic
within a single response system depending on the
nature of the environmental cue and are mediated
by expectancy. That respones may be bi-directional
makes the case for arguing in favour of only an
appetitive mechanism in relapse (Niaura et al.,
1988) inapplicable. Further, until physiological
measures of responsiveness to ARCs are viewed as
part of an interactive system of responses, erroneous
interpretations of the directionality of responses can
be made.
While extinction of CRs to ARCs remains to be
convincingly demonstrated in humans, animal stud-
ies suggest that in theory at least this should be
possible providing adequate information is known
regarding conditioning history and stimulus sali-
ence. Inevitably, the effects of laboratory extinction
procedures will be limited by the problem of
generalization to the natural environment. Never-
theless, conditioning theory and the cue exposure
method provide a useful paradigm to study relapse.
Concepts of arousal, craving and appetitive
responding are oversimplistic, ill-defined and inade-
quate in explaining the observed phenomena in cue
exposure. In particular, craving is an ambiguous
label which is subject to a variety of interpretations
and the influence of attribution. We argue that its
use impedes progress in this field. It remains to be
determined whether the subjective desire or urge to
take a drug is mediated by CAgRs and/or CAntRs.
Moreover, it cannot be assumed, as has been
previously suggested, that physiological responses to
ARCs are covariates of craving. We suspect, how-
ever that the use of the term 'craving' will prove
resistant to extinction.
Throughout the course of this paper we have
pointed to a number of potential research questions
and directions in which the study of cue exposure
should proceed. In summarizing our recommenda-
tions we draw attention to the application of
concepts which have been developed from both
conditioning and cognitive theories of relapse. The
application of expectancy theory to the study of
conditioned learning in alcohol dependence has led
to advances in our understanding of CRs to ARCs.
Future research should extend this cross-fertiliza-
tion of ideas between these two theoretical models.
As stated at the beginning of this review, many of
the theoretical issues raised have direct relevance to
both drug and alcohol dependence.
1. The study of CRs to ARCs in the laboratory
remains an open and potentially valuable area of
research. While previous work has revealed subjec-
tive and psychophysiological responses to environ-
mental cues, little is known about the multivariate
patterning of responses and the factors which may
influence cue salience. The application of a systems
approach to understanding physiological responses
to environmental cues should reduce the possibility
of making erroneous, interpretations about the
directionality of responses. Inevitably such research
in the future will require greater technical sophisti-
cation than has previously been applied. As we have
suggested, concepts such as self-efficacy and cogni-
tive dissonance also deserve further study in terms
of their influence on CRs to ARCs.
2. Subjective responses to environmental cues cannot
be assumed to be indicative of any particular
underlying physiological state or behavioural inten-
tion. As we have argued, the term 'craving' should
be replaced by more precise descriptions of subjec-
tive responses to environmental cues in technical
studies. The study of the effects of context and
attributions in the cue exposure setting is needed to
expand our understanding of physiological and
subjective responses beyond that of a simple reflex-
ive model.
3. The relationship between classical and operant
conditioning in human drug and alcohol dependence
requires to be subjected to a more detailed analysis.
The effect of directionality of CRs to drug and
alcohol-related cues on operant responses is at
present unclear. Study of this interaction in the
laboratory may lead to an experimental model of
relapse which will allow more accurate predictions
to be made about the potential effects of cue
exposure treatment than could be inferred from a
clinical trial. The induction and extinction of CRs to
environmental cues in social drinkers provides a
potentially useful experimental paradigm.
4. Cue exposure without consumption of a priming
dose provides a valid experimental paradigm for the
investigation of CRs to ARCs. Giving alcohol to
alcohol dependent individuals in cue exposure
studies is controversial (Laberg & Ellertsen, 1987)
and complicates the interpretation of physiological
responses due to unconditioned alcohol effects. We
conclude that it is possible to demonstrate CRs to
ARCs without consumption of a priming dose of
alcohol and that this represents a valid and useful
paradigm for the conduct of cue exposure research.
5. Greater emphasis should be placed upon the study
of the basic mechanisms important in relapse. It is
perhaps an unfortunate consequence of the urgent
need to find an effective treatment for drug and
alcohol dependence that so many resources have
been directed towards treatment outcome studies in
spite of a lack of clear evidence to implicate CRs to
environmental cues in relapse. Further, there is
evidence to suggest that extinction of CRs to ARCs
may not necessarily result in a reduced likelihood of
relapse. It could be argued that repeated negative
findings from treatment outcome studies, on the
way to discovery of the important factors mediating
relapse, may have the unwanted effect of turning
attention away from the whole field of research
endeavour in cue exposure, including promising
basic research. Treatment outcome studies should
not be abandoned, but instead allied to basic non-
clinical research, a point which has relevance to the
rest of the addiction research field.
Acknowledgements
We gratefully acknowledge the helpful comments
and suggestions of Professor Griffith Edwards and
Dr Brendan Bradley on an earlier draft of this paper.
Many thanks are also due to Mrs Evelyn Langford
for her expert secretarial assistance. This work was
supported by the Medical Research Council.
References
ANNIS H. M. & DAVIS, C. S. (in press) Relapse prevention,
in: R. K. HESTER & W. R. MILLER (Eds.) Handbook of
Alcoholism Treatment Approaches (New York, Perga-
mon Press).
AzRiN, N. H. & HAKE, D. F. (1969) Positive conditioned
suppression: conditioned suppression using positive
reinforcers as the unconditioned stimuli. Journal of the
Experimental Analysis of Behaviour, 12, pp. 167-173.
BAKER, T. B. , MORSE, E. & SHERMAN, J. E. (1987) The
motivation to use drugs: a psychobiological analysis of
urges, in: P. E. NATHAN et al. (Eds.) Alcohol and
Addictive Behavior, Nebraska Symposium on Motiva-
tion, 1986 (Lincoln, University of Nebraska Press).
BANDURA, A. (1977) Self-efficacy: toward a unifying
theory of behavioural change. Psychological Review, 84,
pp. 191-215.
BANDURA, A. (1981) Self-referent thought: a developmen-
tal analysis of self-efficacy, in: J. H. FLAVELL & L. Ross
(Eds.) Social cognitive development: frontiers and pos-
sible futures (Cambridge, Cambridge University Press).
BANDURA, A. (1982) Self-efficacy mechanism in human
agency, American Psychologist, 37, pp. 122-147.
BAUM, M. (1969) Extinction of an avoidance response
following response prevention: some parametric investi-
gations. Canadian Journal of Psychology, 23, pp. 1-10.
BEAZELL, J. M. & IVY, A. C. (1940) The influence of
alcohol on the digestive tract: a review. Quarterly
Journal of Studies on Alcohol, 1, 45.
BLAKEY, R. & BAKER, R. (1980) An exposure approach to
alcohol ahuss. Behaviour Research and Therapy, 18, pp.
319-325.
BOLLES, R. C. (1972) Reinforcement, expectancy and
learning. Psychological Review, 74, pp. 344-409.
BRADLEY, B. P. & MOOREY, S. (1988) Extinction of
craving during exposure to drug-related cues: three
single case reports. Behavioural Psychotherapy, 16, pp.
45-57.
CACIOPPO, J. T. & PETTY, R. E. (1982) A biosocial model
of attitude change, in: J. T. CACIOPPO & R. E. PETTY
(Eds.) Perspective in Cardiovascular Psychophysiology
(New York, Guildford).
CARPENTER, J. (1957) The effects of alcoholic beverages
on skin conductance: an exploratory study. Quarterly
Journal of Studies on Alcohol, 18, pp. 1-18.
CHANDLER, B. C , PARSONS, O. A. & VEGA, A. (1975)
Autonomic functioning in alcoholics: a study of heart
rate and skin conductance. Journal of Studies on
Alcohol, 36, 5, pp. 566-577.
CHANEY, E. F. , O'LEARY, M. R. & MARLATT, G. A. (1978)
Skill training with alcoholics. Journal of Consulting and
Clinical Psychology, 46, pp. 1092-1104.
CHANEY, E. F. , ROSZELL, D. K. & CUMMINGS, C. (1982)
Relapse in opiate addicts: a behavioural analysis, .(4(fdic-
tive Behaviours, 7, pp. 291-297.
CHILDRESS, A. R. , MCLELLAN, A. T. & O' BRIEN, C. P.
(1984) Measurement and extinction of conditioned
withdrawal like responses in opiate-dependent patients,
in: Problems of drug dependence, NIDA Research Mono-
graph, 49, (Washington, DC, DHHS).
CHILDRESS, A. R., MCLELLAN, A. T. & O' BRIEN, C. P.
(1986a) Abstinent opiate abusers exhibit conditioned
craving, conditioned withdrawal and reductions in both
through extinction, British Journal of Addiction, 81, 5,
pp. 655-660.
CHILDRESS, A. R., MCLELLAN, A. t". & O' BRIEN, C. P.
(1986b) Conditioned responses in a methadone popula-
tion: a comparison of laboratory, clinic and natural
setting. Journal of Substance Abuse Treatment, 3, pp.
173-179.
CHILDRESS, A. R., MCLELLAN, A. T. & O' BRIEN, C. P.
(1986c) Nature and incidence of conditioned responses
in a methadone population: a comparison of laboratory
clinic and naturalistic setting, in: Problems of Drug
Dependence 1985, NIDA research Monograph, 67, pp.
366-372 (Washington, DC, DHHS).
CHILDRESS, A. R., MCLELLAN, A. T., EHRAM, R. &
O' BRIEN, C. P. (1986d) Classically conditioned re-
sponses in opioid and cocaine dependence: a role in
relapse? Presented at NIDA technical review meeting:
Learning Factors in Substance Abuse, 3-4 November
1986.
CHILDRESS, A. R., MCLELLAN, A. T., NOTALE, M. &
O' BRIEN, C. P. (1987) Mood states can elicit condi-
tioned withdrawal and craving in opiate abuse patients,
in: Problems of Drug Dependence 1986, NIDA Research
Monograph, 76, pp. 137-144 (Washington, DC,
DHHS).
CHOTLOS, J. W. & GOLDSTEIN, G. (1967) Psychophysiolo-
gical responses to meaningful sounds. Journal of Ner-
vous and Mental Disease, 145, pp. 315-325.
CONDIOTTE, M. M. & LiCHTENSTEIN, E. (1981) Self-
efficacy and relapse in smoking cessation programs.
Journal of Consulting and Clinical Psychology, 49, pp.
648-658.
CooNBY, N. L., BAKER, L. H. , POMERLEAU, O. F. &
JOSEPHY, B. (1984) Salivation to drinking cues in
alcohol abuse: towards the validation of a physiological
measure of craving, ^ddictroe Behaviours, 9, pp. 91-94.
COONEY, N. L., GiLLESPIE, R. A., BAKER, L. H. & KAPLAN,
R. F. (1987) Cognitive changes after alcohol cue
exposure. Journal of Consulting and Clinical Psych-
ology, 55(2), pp. 150-155.
CooPERSMiTH, S. (1964) Adaptive reactions of alcoholics
and nonalcoholics. Quarterly Journal of Studies on
Alcohol, 25, pp. 262-278.
CORTY, E., O'BWEN, C. P. & MANN, S. (1988) Reactivity
to alcohol stimuli in alcoholics: is there a role for
temptation? Drug and Alcohol Dependence, 21, pp.
29-36.
CROWELL, C. R. , HINSON, R. B. & SIEGEL, S. (1981) The
role of conditional drug responses in tolerance to the
hypothermic effects of ethanol, Psychopharmacology,
73, pp. 51-54.
DAFTERS, R. & ANDERSON, G. (1982) Conditioned toler-
ance to the tachycardia effect of ethanol in humans,
Psychopharmacology, 78, p. 365.
Di CLEMENTE, C. C. (1981) Self-efficacy and smoking
cessation maintenance. Cognitive Therapy and Research,
5, pp. 175-187.
DocTER, R. F. & BERNAL, M. E. (1964) Immediate and
prolonged psychophysioiogical effects of sustained alco-
hol intake in alcoholics. Quarterly Journal of Studies on
Alcohol, 25, p. 438.
DocTER, R. F. & PERKINS, R. B. (1960) The effects of
ethyl alcohol on automomic and muscular responses in
humans. Quarterly Journal of Studies on Alcohol, 22,
p. 374.
DocTER, R., NAITOH, P. & SMITH, J. C. (1966) Electroen-
cephaiographic changes and vigilance behaviour during
experimentally induced intoxication with alcoholic sub-
jects. Psychosomatic Medicine, 28, pp. 605-615.
DoLiNSKY, Z. S., MORSE, D. E. , KAPLAN, R. F. , MEYER,
R. E. et al. (1987) Neuroendocrine, psychophysiological
and subjective reactivity to an alcohol placebo in male
alcoholic patients. Alcoholism: Clinical and Experimen-
tal Research, 11(3), pp. 296-300.
DONOVAN, D. M. & CHANEY, E. F. (1985) Alcoholic
relapse prevention and intervention: models and
methods, in: G. A. MARLATT & J. R. GORDON (Eds.)
Relapse Prevention: Maintenance Strategies in the Treat-
ment of Addictive Behaviors (New York, Guildford).
EiKELBOOM, R. & STEWART, J. (1982) Conditioning of
drug induced physiological responses. Psychological
Review, 89, pp. 507-528.
ELLIOT, R. (1974) The motivational significance of heart
rate, in: P. A. OBRIST, A. H. BLACK, J. BRENER & L. V.
DICARA (Eds.) Cardiovascular psychophysiology: cur-
rent issues in response mechanisms, biofeedback and
methodology (Chicago, Aldine).
ENGLE, K. B. & WILLIAMS, T. K. (1972) Effect of an
ounce of vodka on alcoholic's desire for alcohol.
Quarterly Journal of Studies on Alcohol, 33, pp.
1099-1105.
ERIKSEN, L. & GOTESTAM, K. G. (1984) Conditioned
abstinence in alcoholics: a controlled experiment. Inter-
national Journal of the Addictions, 19(3), pp. 287-294.
FESTINGER, L. (1957) A Theory of Cognitive Dissonance
(Stanford, Stanford tJniversity Press).
FREEMAN, H. L. & KENDRICK, D. C. (1960) A case of cat
phobia, British Medical Journal, ii, pp. 497-502.
GERARD, H. B. (1967) Choice difficulty, dissonance, and
the decision sequence. Journal of Personality, 35, pp.
91-108.
GREENBERG, L. A. & CARPENTER, J. A. (1957) The effect
of alcoholic beverages on skin conductance and emo-
tional tension. I. Wine, whiskey and alcohol. Quarterly
Journal of Studies on Alcohol, 18, pp. 190-204.
GRIFFITHS, R. , BIGELOW, G. & LIEBSON, I. (1976)
Facilitation of human tobacco self-administration by
ethanol: a behavioural analysis. Journal of the Experi-
mental Analysis of Behaviour, 25, pp. 279-292.
HEATHER, N. & STALLARD, A. (1989) Does the Marlatt
model underestimate the importance of conditioned
craving in the relapse process? in: M. Gossop (Ed.)
Relapse and Addictive Behaviour (London, Routledge).
HODGSON, R. J. & RANKIN, H. J. (1976) Modification of
excessive drinking by cue exposure. Behaviour Research
and Therapy, 14, pp. 305-307.
HODGSON, R. J. & RANKIN, H. J. (1982) Cue exposure and
relapse prevention, in: P. NATHAN & W. HAY (Eds.)
Case studies in the Behavioural Modification of Alcohol-
ism (New York, Plenum Press).
HODGSON, R. , RANKIN, H. & STOCKWELL, T . (1979)
Alcohol dependence and the priming effect. Behaviour
Research and Therapy, 17, pp. 379-387.
HOLMBERG, G. & MARTENS, S. (1955) Electoencephalo-
graphic changes in man correlated with blood alcohol
concentration and some other conditions following
standardized ingestion of alcohol. Quarterly Journal of
Studies on Alcohol, 16, p. 411.
HiKSON, R. E. & SIEGEL, S. (1983) Anticipatory hyperex-
citabiiity and tolerance to the narcotizing effect of
morphine in the rat. Behavioural Neuroscience, 97, pp.
759-767.
KAPLAN, R. F. , MEYER, R. E. & STOEBEL, C. F. (1983)
Alcohol dependence and responsivity to an ethanol
stimulus as predictors of alcohol consumption, British
Journal of Addiction, 78, pp. 259-267.
KAPLAN, R. F. , MEYER, R. E. & VIRGILIO, L. M. (1984)
Physiological reactivity to alcohol cues and the aware-
ness of an alcohol effect in a double blind placebo
design, British Journal of Addiction, 79, pp. 439-442.
KAPLAN, R. F. , COONEY, N. L. , BAKER, L. H. , GILLESPIE,
A., MEYER, R. E. & POMERLEAU, O. F. (1985)
Reactivity to alcohol-related cues: physiological and
subjective responses in alcoholics and non-problem
drinkers. Journal of Studies on Alcohol, 46, 4, pp.
267-272.
KENNEDY, D. A. (1971) Pupilometrics as an aid in the
assessment of motivation, impact of treatment and
prognosis of chronic alcoliolics. Unpublished doctoral
dissertation. University of Utah.
KiSSIN, B., SCHENKER, V. & SCHENKER, A. C. (1959) The
acute effects of ethyl alcohol and chloropromazine on
certain physiological functions in alcoholics. Quarterly
Journal of Studies on Alcohol, 20, p. 480.
KRANK, M. D. , HINSON, R. E. & SIEGEL, S. (1981)
Conditional hyperalgesia is elicited by environmental
signals of morphine. Behavioural and Neural Biology,
32, pp. 148-157.
LABERG, J. C. (1986) Alcohol and expectancy: subjec-
tive, psychophysiological and behavioural responses to
alcohol stimuli in severely, moderately and non-depen-
dent drinkers, British Journal of Addiction, 81, pp.
797-808.
LABERG, J. C. & ELLERTSEN, B. (1987) Psychophysiologi-
cal indicators of craving in alcoholics: effects of cue
exposure, British Journal of Addiction, 82, pp.
1341-1348.
LACEY, J. I. (1959) Psychophysiological approaches to the
evaluation of psychotherapeutic processes and outcome,
in: E. RUBENSTEIN & M. B. PARLOFF (Eds.) Research in
Psychotherapy (Wasington, DC, American Psychologi-
cal Association).
LACEY, J. I. (1967) Somatic response patterning and stress:
some revisions of activation theory, in: M. H. APPLEY &
-R. TRUMBULL (Eds.) Psychological Stress, pp. 14-42
(New York, Appleton-Century-Crofts).
LAWSON, D. M. , WILSON, G. T. , BRIDDELL, D. W. & IVES,
C. C. (1976) Assessment and modification of alcoholic's
drinking beiiaviour in controlled laboratory settings: a
cautionary note. Addictive Behaviours, 1, pp. 299-303.
LE, A. D. , POULOS, C. X. & CAPPELL, H. (1979)
Conditioned tolerance to the hypothermic effect of ethyl
alcohol, Science, 206, pp. 1109-1110.
LEGARDA, J. (1989) Subjective and psychophysiological
effects of exposure to drug-related cues in detoxified
heroin addicts, ch. 5, PhD. Thesis, University of London.
LEVENSON, R. W. , SHER, K. J., CROSSMAN, L. M. ,
NEWMAN, J. & NEWLIN, D. B. (1980) Alcohol and stress
response dampening: pharmacological effects, expec-
tancy and tension reduction. Journal of Abnormal
Psychology, 89, pp. 528-538.
LiPSCOMB, T. R. & NATHAN, P. E. (1980) Effect of family
history of alcoholism, drinking pattern, and tolerance on
blood alcohol level discrimination. Archives of General
Psychiatry, 37, pp. 571-576.
LiTT, M. D., CoONEY, N. L., KADDEN, R. M. & GAUPP, L.
(1989) Reactivity to alcohol cues and induced mood in
alcoholics (in preparation).
LOLORDO, V. M. (1971) Facilitation of food reinforced
responding by a signal for response independent food.
Journal of the Experimental Analysis of Behaviour, 15,
pp. 49-55.
LOLORDO, V. M., MACMILLAN, J. A. & RiLEY, A. L.
(1974) The effects upon food reinforced key pecking
and treadle pressing of auditory and visual signals for
response independent food. Learning and Motivation, 5,
pp. 24-41.
LuDWIG, A. M. & WlKLER, A. (1974) Craving and relapse
to drinking. Quarterly Journal of Studies on Alcohol, 35,
pp. 108-130.
LuDwiG, A. M., WiKLER, A. & STARK, L. H. (1974) The
first drink: psychobiological aspects of craving. Archives
of General Psychiatry, 30, pp. 539-547.
MACKINTOSH, N. J. (1983) Conditioning and Associative
Learning (Oxford, Clarendon Press).
MALMO, R. B. (1959) Activation: a neuropsychological
dimension. Psychological Review, 66, pp. 367-386.
MANSFIELD, J. G., CUNNINGHAM, C. L. (1980) Condition-
ing and extinction of tolerance to the hypothermic effect
of ethanol in lats. Journal of Comparative Physiological
MARKS, L M. , HODGSON, R. & RACHMAN, S. (1975)
Treatment of chronic obsessive-compulsive neurosis by
in vivo cue exposure: a two year follow-up and issues in
treatment, British Journal of Psychiatry, 127, pp.
349-364.
MARLATT, G. A. (1978) Craving for alcohol, loss of
control and relapse: a cognitive-behavioural analysis, in:
P. E. NATHAN, G. A. MARLATT & T. LABERG (Eds.)
Alcoholism: Nezv Directions in Behavioural Research and
Treatment (New York, Plenum).
MARLATT, G. A. (1985a) Situational determinants of
relapse and skill-training interventions, in: G. A.
MARLATT & J. R. GORDON (Eds.) Relapse Prevention:
Maintenance Strategies in the Treatment of Addictive
Behaviours (New York, NY, Guildford).
MARLATT, G. A. (1985b) Cognitive processes in alcohol
use: expectancy and the balanced placebo design, in: N.
K. MELLO (Ed.) Advances in Substance Abuse, 1
(Greenwich, Conn., JAI).
MARLATT, G. A. (1988) Cue exposure and relapse
prevention in the treatment of addictive behaviours.
Discussion paper presented at the Cue Exposure in
Addictive Behaviours Symposium, Behaviour Therapy
World Congress, Edinburgh, September, 1988.
MARLATT, G. A. & ROSENHOW, D. R. (1980) Cognitive
processes in alcohol use: expectancy and the balanced
placebo design, in: N. K. MELLO (Ed.) Advances in
Substance Abuse, 1 (Greenwich, Conn., JAI).
MARLATT, G. A. & ROSENHOW, D. R. (1981) The think-
drink effect. Psychology Today, 15, pp. 60-93.
MARLATT, G. A., DEMMING, B. & RIED, J. B. (1973) Loss of
control drinking in alcoholics: an experimental analogue.
Journal of Abnormal Psychology, 81, pp. 223-241.
McAuLlFFE, W. E. (1982) A test of Wikler's theory of
relapse due to conditioned withdrawal sickness. Interna-
tional Journal of the Addictions, 17, pp. 19-23.
MCLELLAN, A. T. , CHILDRESS, A. R., EHRMAN, R. W. &
O' BRIEN, C. P. (1986) Extinguishing conditioned re-
sponses during treatment for opiate dependence: turning
laboratory findings into clinical procedures. Journal of
Substance Abuse Treatment, 3, pp. 33-40.
MELCHIOR, C. L. & TABAKOFF, B. (1981) Conditioned
tolerance to the hypothermic and hypnotic effects of
ethanol in mice. Federation Proceedings of the Federation
of American Social Experimental Biology.
MELCHIOR, C. L. & TABAKOFF, B. (1982) Environment
dependent tolerance to the lethal effects of ethanol.
Alcohol: Clinical & Experimental Research, 6, p. 306.
MELCHIOR, C. L. & TABAKOFF, B. (1984) A conditioning
model of alcohol tolerance, in: M. GALANTER (Ed.)
Recent Developments in Alcoholism, 2, pp. 5-16.
MENDELSON, J. H. & LADOU, J. (1964) Experimentally
induced chronic intoxication and withdrawal in alcohol-
ics. Part 1. Background and experimental design.
Quarterly Journal of Studies on Alcohol, Suppl. No. 2,
p. 1.
MONTI, P. M., BINKOFF, J. A., ABRAMS, D. B. , ZWICK,
W. R. et al. (1987) Reactivity of alcoholics and non-
alcoholics to drinking cues. Journal of Abnormal
NEWLIN, D. B. (1984) The conditioned compensatory
response to alcohol placebo in humans, Psychophysiol-
ogy, 21, p. 590.
NEWLIN, D. B. (1985a) The antagonistic placebo response
to alcohol cues. Alcoholism: Clinical and Experimental
Research, 9(5), pp. 411-416.
NEWLIN, D. B. (1985b) Offspring of alcoholics have
enhanced antagonistic placebo response. Journal of
Studies on Alcohol, 46(6), pp. 490-494.
NEWLIN, D.B. (1986) Conditioned compensatory response
to alcohol placebo in humans, Psychopharmacology, 88,
pp. 247-251.
NiAURA, R. S., ROSENHOW, D. J., BiNKOFF, J. A., MONTI,
P. M. et al. (1988) Relevance of cue reactivity to
understanding alcohol and smoking relapse, Journal of
Abnormal Psychology, 97, pp. 133-152.
NisBETT, R. E. & WILSON, T. D. (1977) Telling more than
we know: verbal reports on mental processes. Psycholo-
gical Review, 84, pp. 231-259.
PiCKENS, R., BiGELOW, F. & GRIFFITHS, R. (1973) An
experimental approach to treating chronic alcoholism: a
case study and one year follow-up. Behaviour Research
and Therapy, 11, pp. 321-325.
PoMERLEAU, O. F. (1981) Underlying mechanisms in
substance abuse: examples from research on smoking.
Addictive Behaviours, 6, pp. 187-196.
POMERLEAU, O. F., FERTIG, J., BAKER, L. & COONEY, N.
(1983) Reactivity to alcohol cues in alcoholics and non-
alcoholics: implications for a stimulus control analysis of
drinking. Addictive Behaviours, 8, pp. 1-10.
QUANTY, M. B. & BECKER, L. A. (1974) Physiological
indices of dissonance arousal and reduction in a stressful
situation (Columbia, University of Missouri).
RACHMAN, S. & HODGSON, R. (1980) Obsessions and
Compulsions (New Jersey, Prentice Hall, Englewood-
Cliffs).
RAFFA, R. B. , PORRBCA, F. , COWAN, A. & TALLARIDA, R. J.
(1982) Evidence for the role of conditioning in the
development of tolerance to morphine-induced inhibi-
tion of gastrointestinal motility in rats. Federation
Proceedings, 41, pp. 1317.
RANKIN, H. (1981) The behavioural assessment and
treatment of alcoholism, PhD thesis. University of
London, pp. 236-307.
RANKIN, H. , HODGSON, R. & STOCKWELL, T. (1979) The
concept of craving and its measurement. Behaviour
Research and Therapy, 17, pp. 389-396.
RANKIN, H. , HODGSON, R. & STOCKWELL, T . (1983) Cue
exposure and response prevention with alcoholics: a
controlled trial. Behaviour Research and Therapy,
21(4), pp. 435-446.
RANKIN, H. , STOCKWELL, T. & HODGSON, R. (1982) Cues
for drinking and degrees of alcohol dependence, British
Journal of Addiction, 77, 287-296.
REISS, S. (1980) Pavlovian conditioning and human fear: an
expectancy model. Behaviour Therapy, 11, pp. 380-396.
RESCORLA, R. A. & LoLoRDO, V. M. (1965) Inhibition of
avoidance behaviour. Journal of Comparative Physio-
logical Psychology, 59, pp. 406-412.
RESCORLA, R. A. & SOLOMAN, R. L. (1967) Two-process
learning theory: relationships between Pavlovian condi-
tioning and instrumental learning. Psychological Review,
74, pp. 151-182.
RESCORLA, R. A. & WAGNER, A. R. A. (1972) A theory of
Pavlovian conditioning: variations in the effectiveness
of reinforcement and non-reinforcement, in: A. H.
BLACK & W. F. PROKASY (Eds.) Classical Conditioning
II (New York, Appleton-Century-Crofts).
RiST, F. & WATZL, H. (1983) Self assessment of relapse
risk and assertiveness in relation to treatment outcome
of female alcoholics. Addictive Behaviours, 8, pp.
121-127.
RITCHIE, J. M. (1965) The aliphatic alcohols, in: L. S. B.
GOODMAN & A. GILMAN (Eds.) The Pharmacological
Basis of Therapeutics, pp. 143-158 (New York, Mac-
Millan).
ROTH, G. M. & SHEARD, C. (1947) Effect of smoking on
the vasodilation produced by the oral administration of
95 per cent ethyl alcohol or a substantial meal, American
Heart Journal, 33, p. 654.
SCHACHTER, S. & SiNGER, J. E. (1962) Cognitive, social,
and physiological determinants of emotional state.
Psychological Review, 69, pp. 379-394.
SCHWARTZ, B. & GAMZU, E. (1977) Pavlovian control of
operant behaviour: an analysis of autoshaping and its
implications for operant conditioning, in: W. K. HONIG
& J. F. R. STADDON (Eds) Handbook of Operant
Behavior (New Jersey, Prentice Hall).
SCHWARTZ, G. E. (1982) Cardiovascular psychophysiol-
ogy: a systems perspective, in: J. CACIOPPO & R. E.
PETTY (Eds) Perspectives in Cardiovascular Psychophy-
siology (New York, Guildford).
SHAPIRO, A. P., NATHAN, P. E. (1986) Human tolerance to
alcohol: the role of Pavlovian conditioning processes,
Psychopharmacology, 88, pp. 90-95.
SlEGEL, S. (1975) Evidence from rats that morphine
tolerance is a learned response. Journal of Comparative
Physiological Psychology, 89, pp. 498-506.
SiEGEL, S. (1978) Tolerance to the hyperthermic effect of
morphine in the rat is a learned response. Journal of
Comparative Physiological Psychology, 92, pp.
1137-1149.
SlEGEL, S. (1988) Drug anticipation and drug tolerance,
in: M. LADER (Ed.) Psychopharmacology of Addiction
(New York, Oxford University Press).
SlEGEL, S., HiNSON, R. E. & KRANK, M. D. (1979)
Modulation of tolerance to the lethal effect of morphine
by extinction. Behavioural and Neural Biology, 25, pp.
257-262.
SlEGEL, S., SHERMAN, J. E. & MITCHELL, D. (1980)
Extinction of morphine analgesic tolerance. Learning
and Motivation, 11, pp. 289-301.
SOLOMON, R. L. (1977) An opponent-process theory of
acquired motivation: IV. The affective dynamics of
addiction, in: J. MASER & M. E. P. SELIGMAN (Eds.)
Psychopathology: Experimental Models (San Francisco,
Freeman).
SOLOMON, R. L. & CORBITT, J. D. (1974) An opponent-
process theory of motivation: I, temporal dynamics of
affect. Psychological Review, 81, pp. 119-145.
STAIGER, P. k. & WHITE, J. M. (1988) Conditioned
alcohol-like and alcohol-opposite responses in humans,
Psychopharmacology, 95, pp. 87-91.
STEWART, J., DE Wrr, H. & EIKELBOOM, R. (1984) Role of
unconditioned and conditioned drug effects in the self
administration of opiates and stimulants. Psychological
Review, 91, pp. 251-268.
STOCKWELL, T. R. , HODGSON, R. J., RANKIN, H. J. &
TAYLOR, C. (1982) Alcohol dependence, beliefs and the
priming effect. Behaviour Research and Therapy, 20,
pp. 513-522.
WlKLER, A. (1965) Conditioning factors in opiate addic-
tion and relapse, in: D. I. WIHER & G. KASSEBAUM
(Eds.) Narcotics (New York, McGraw-Hill).
WILLIAMS, D. R. (1965) Classical conditioning and
incentive motivation, in: W. F. PROKASY (Ed.) Classical
Conditioning (New York, Appleton Century Crofts).
WISE, R. A. & BOZARTH, M. A. (1987) A psychomotor
stimulant theory of addiction. Psychological Review, 4,
pp. 469-492.

Conditioned Learning in Alcohol Dependence

Enviado por

Dados do documento

Descrição original:

Direitos autorais

Formatos disponíveis

Compartilhar este documento

Compartilhar ou incorporar documento

Opções de compartilhamento

Você considera este documento útil?

Este conteúdo é inapropriado?

Direitos autorais:

Formatos disponíveis

Conditioned Learning in Alcohol Dependence

Enviado por

Direitos autorais:

Formatos disponíveis

British Journal of Addiction (1990) 85, 725-743

Você também pode gostar