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Pharmacology of Perception
Structure in the Brain
Brain & spinal cord Neuron Dendritic spines
-
+
+
+
+
Signal goes from the
cell body down the axon
4 (+ or -)
Drug Action
1
2
1
3 7
7 3
5
4 (+ or -)
Action at the receptor
1) drugs generally act by mimicking (agonists) or
blocking (antagonists) natural neurotransmitters
2) Specific to receptor subtypes
Natural
Agonist Compound Antagonist
Signal (+ or -) (+ or -)
Receptor specificity
Each neurotransmitter can only act on specific receptors (lock and key)
In reality receptors are not simple “open-shut” gates… They have complex
structures and it is often a small change in their shape that will “open” a
channel, or cause it to “do its thing”.
Summary
2h 45min 5h 45min 8h
Hallucinogens also cause illusions of motions. Objects and patterns are often seen
to move, without actually changing location – similar to the sense of motion that
occurs when your eyes move over this pattern (Note that different mechanisms are
likely to be responsible for this illusion and the action of hallucinogens).
Psilocybin (psilocin)
H3C
CH3
N
OH
Psilcybe mushrooms N
(“Magic” mushrooms)
H
Psilocin
N
H N
N N
H
H
DMT LSD
Serotonin (5-HT)
All 5-HT in the brain comes THALAMUS CORTEX
from the raphe nucleus in
the brainstem, from there it NUCLEUS ACCUMBENS
HO
HIPPOCAMPUS
N
H CEREBELLAR
CORTEX
RAPHE NUCLEUS
(rostral & dorsal)
Many receptor subtypes:
5-HT1 (A, B, D, E & F)
5-HT2 (A, B, & C)
5-HT3
5-HT4
5-HT5 (A & B) 5-HT is associated with Mood, Sleep, Appetite,
5-HT6? Clinical Psychosis & Hallucinogens!!
5-HT7?
Location of 5-HT2A receptors
Cortex
Thalamus
- Ventral Striatum
- Hippocampus
- Amygdala
Serotonin and Perception
-- Hallucinogen experiments --
Hallucinogens as a research tool
or or
or or
Coherent motion
(global motion)
MT seems to be
necessary for
Temporal Lobe V1 coherent motion
Cerebellum detection
3) Clinical
Processing of global, but not local, motion direction is deficient in schizophrenia
- Chen Y, Nakayama K, Levy D, Matthysse S and Holzman P. (2003) Schizophr Res 61:215-227.
Results
Local motion detection Coherent motion
is unaffected detection is impaired
30 30
Coherence Sensitivity
Contrast Sensitivity
20 20
*
10 10
2 2
Pre-test Peak ~ 120min Pre-test Peak ~ 120min
Placebo
Psilocybin
Summary
- High level but not low level motion processing was
impaired.
- In line with Schizophrenia findings.
- Successful transfer of information from retina, LGN to V1
Future Questions
- If hallucinogens do not change sensitivity to the incoming
sensory information, where does the feeling of increased
sensitivity to contrast, motion & colour come from?
Take Home Message
1) Pharmacology is relevant!
Activity of neurons is crucial, but it is the pattern of activity that
determines our moment to moment state depends on
neurotransmitters.