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By,
Dr. Manoj Upadhya,
SKBCOP, Kamptee
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It is a degenerative disorder of Central Nervous System
Extensive degradation of dopaminergic neurons of the
Substantia nigra.
o Genetic
o Environmental triggers
o Excitotoxicity (excess Glutamate)
o Oxidative stress
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Akinesia: Difficulty in
initiating movement
Bradykinesia: Slowness of
movement
Rigidity: Muscular stiffness
Tremors: Shaking
movements of periphery
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Muscarnic agonsits
(Tremorine and Oxotremorine)
Tremor, Ataxia, Spasticity, Salivation,
Lacrimation, Hypothermia
Anticholinergic drugs
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Test compound or standard
(5 mg/kg benzatropine mesilate p.o.) is administered
(1 h)
Oxotremorine (0.5 mg/kg s.c.)
Rectal temperature is measured before administration and
1, 2 and 3 h after oxotremorine
is scored after oxotremorine administration for 10sec after every 15 min for 1 h,
are scored 15min and 30min after oxotremorine inj.
Scoring scale
Tremor, Lacrimation or Salivation Score
Absent 0
Slight 1
Medium 2
Severe 3
Procedure:
Mice 18-22 g
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Evaluation
Hypothermia
The average values are compared statistically with the control group
Tremor
The total score is summarized. The number in the treated group are
expressed as percentage of number of control group
Salivation and Lacrimation
The total score is summarized. The number in the treated group are
expressed as percentage of number of control group
The oxotremorine antagonism has been proven to be a
reliable method for testing central anticholinergic
activity.

The overt isomorphism between the animal model and
the symptoms of Parkinsons disease recommend this
test for screening of anti-Parkinson drugs.
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N-MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
Partial destruction of basal ganglia
Syndrome that resembles Parkinsons disease
(Akinesia, rigidity, postural tremor, fixed posture, eyelid
closure, drooling)
Scoring of severity is done trained observer on the
scale of 0 (normal) to 17 (max severity) .
Evaluation
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Reserpine induces depletion of central catecholamine stores.
Sedative effect followed by signs of
eyelid ptosis, hypokinesia, rigidity, catatonia, and immobility
Dopamine agonists
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Procedure:
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Mice 20-25 g
Reserpine (5 mg/kg i.p.) is administered
(24 h)
Test drug or standard
Signs are observed in Perspex container (30 x 26 cm, 20 cm high)
Horizontal movements are recorded for 10 min
Raring and grooming episodes are registered by an experienced observer.
(30 min)
Evaluation
Locomotor activity and grooming scores of treated animals
are compared with control and vehicle treated animals.
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Unilateral lesions of dopaminargic nigrostriatal pathway by
neurotoxin 6-hydroxydopamine (6-OHDA)
Hypersensitivity of postsynaptic dopaminargic receptors in
striatum of lesioned side.
The rat rotates ipsilateral when indirect acting compound like
amphetamine is administered.
While rotates contralateral when direct acting dopamine
agonist like apomorphine or dopamine precursor L-dopa is
given.
Procedure:
W. Rats 200-250 g
Rat skull fixed in stereotaxic frame
Coordinates positioned according to atlas
2mm diameter hole is drilled by using electrical drill
(Care not to damage the meninges)
(Anasthesia)
30 gauge stainless-steel cannula is aimed at anterior zona compacta of substantia nigra
8 g of 6-OHDA in 4 L of saline is injected at the rate of 1 L/min
Wound is closed and animal is allowed to recover for several weeks
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Evaluation
Percent change of drug turns from control turns is
recorded.
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Elevated body swing test as a measure of
asymmetrical motor behavior of hemiparkinsonian
animals in drug free state
Procedure:
W. Rats 200-250 g
Rat skull fixed in steriostaxic frame
Coordinates positioned for substansia nigra according to atlas
2mm diameter hole is drilled by using electrical drill
(Care, not to damage the meninges)
(Anasthesia)
30 gauge stainless-steel cannula is aimed at left substantia nigra
8 g of 6-OHDA in 4 L of saline containing 0.02 % ascorbic acid is injected at the rate of
1 L/min and needle is left for more 5 min before retraction
Wound is closed and animal is allowed to recover for one week
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Rat is rested on floor with all 4 pows on the ground
Rat is held above 2.5 cm from the base of its tail and elevated 2.5 cm above the surface on
which it is being rested
A swing is recorded when animal moves its head out of the vertical axis to either side
Swings are counted for 60s in 15s segments
Swings to each side (ipsilateral or contralateral) are counted and rcorded as percentage of total
swings
TWO way ANOVA is used to analyze swing behavior data across the 15s segments
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Paxinos, G., and Watson, C. The Rat Brain in
Stereotaxic. Coordinates, 6th ed. Elsevier/Academic
Press, New York, 2007
Vogel H G, Drug Discovery and Evaluation, Pharmacological
Assays, Springer-Verlag Berlin Heidelberg 2002