1. Dr. Salim Sheikh
1st year PG,Dept. of Pharmacology,
VMMC & Safdarjung Hospital, delhi
drsalimsheikh@yahoo.com

2. 

Understanding psychosis
Newer targets or hypothesis

Validity of an model

Ideal animal model

Screening models & methods

Concept of latent inhibition

3. 
symptom of mental illnesses c/b a distorted or non-existent sense of
reality.

Common psychotic disorders include
*schizophrenia
*mood disorders with psychotic features
*substance-induced psychosis

4. * brief psychotic disorder
*delusional disorder
*schizoaffective disorder
*dementia with psychotic features
*delirium with psychotic features

5. Positive symptoms
(common to all)
Negative symptoms
(specific to szp)
Cognitive symptoms
(specific to szp)
Hallucinations
apathy
working memory
delusions
avolition
processing speed
disorganized speech
alogia
social cognition
disorganized or
agitated behavior
anhodenia
problem solving test

6. 
Drugs, that are able to reduce psychotic symptoms in a wide
variety of conditions, (including schizophrenia)

Typical

Atypical
produces minimal or absent EPS

7. 
1 . Phenothiazines
Aliphatic side :Chlorpromazine,Triflupromazine
Piperidine :Thioridazine
Piperazine :TrifluoperaziL, Fluphenazine

2. Butyrophenones --Haloperidol Trifluperidol ,Penfluridol

3. Thioxanthenes—Flupenthixol

4.Other heterocyclics--Pimozide, Loxapine

5. Atypical--Trifluperazine ,Clozapine,, Risperidone,
Olanzapine, Quetiapine, Aripiprazole, Ziprasidone

8. 
By Carlsson, that postsynaptic DA D2 receptor antagonism
was the common mechanism

reserpine exerted its effects through depletion of monoamines
from presynaptic nerve terminals

high risk for drug-induced psychosis among substances that
directly increased synaptic dopamine availability,

10. 

does not account for the cognitive deficits associated with
schizophrenia (pre-frontal cortex)
does not explain the psychotomimetic effects
-agonists of other pathways 5-HT2
-antagonists of NMDA glutamate receptor.

12. 
NMDA receptors

Antagonism of the 5-HT2 receptor

glutamate and 5-HT7 receptor subtypes

receptors for gamma-aminobutyric acid (GABA)

acetylcholine (M2 polymorphism)

peptide hormone receptors (e.g., oxytocin )

13. 
excessive DA in mesolimbic dopamine pathways.

decreased DA D1 activity in prefrontal cortex (PFC)

In substance-induced psychotic disorders
*directly increase postsynaptic DA activity
*inhibition of presynaptic DA reuptake
*increased DA availability

14. 
deficiency in cholinergic neurotransmission
*due to anticholinergic properties of medications
*age- or disease-related neuronal loss (or both)

Certain environmental exposures
*fetal second-trimester viral and nutritional insults
*birth complications
*substance abuse in the late teen or early adult years

15. 
NMDA antagonists
decrease the glutamate-mediated tonic inhibition
of DA
release in the mesolimbic DA pathway

Glutamate NMDA receptor stimulation facilitates mesocortical
DA release

16. 
mutations or polymorphisms of many genes
*neuregulin 1
*(Val{108/158}Met polymorphism of COMT
*dystrobrevin binding protein 1 or dysbindin,
*nicotinic neurotransmission
*disrupted-in-schizophrenia-1
*copy number variants
*epigenetic changes disruptions in DNA methylation

17. Construct validity refers to the disease relevance of the
methods by which a model is constructed.
1. genetic mutation
2. by altering the expression or function of particular
proteins, biochemical pathways or neural circuits
3. exposure of an animal to a environmental risk factor
or known disease causing agent.

18. 
Face validity indicates that a model recapitulates
anatomical
Biochemical
neuropathological or
behavioral features of a human disease.

Predictive validity signifies that a model responds to
treatments in a way that predicts the effects of those treatments
in humans.

19. 1.
Should have relevance to the clinical condition.
2. The behavioral paradigm used to index the action of APDs
can be used in rats and humans
3. The model should be selective and specific to APDs differing
in their in vitro and in vivo pharmacology.

20. 4. The model can dissociate between typical and atypical APDs.
5. The model does not require previous pharmacological
manipulations to manifest the behavioral index of
antipsychotic activity.
6. The model can shed light on the mechanisms of action of
APDs.

21.  Behavioral
 Tests

tests
based on the mechanism of action
In vitro methods // ex-vivo tests

22. 
Golden hamster test

Influence on behavior of the cotton rat

Artificial hibernation in rats

Catalepsy in rodents

Pole climb avoidance in rats

Foot-shock induced aggression in mice

Brain self stimulation

23. PURPOSE AND RATIONALE

Innate behavior of species (Mesocricetus auratus)

The aggressive behavior of male golden hamsters is suppressed
by neuroleptics in doses which do not impair motor function

24. 
PROCEDURE

Caging of 10-20 golden hamsters , avg. 60gms @2 weeks

Fighting behaviour seen
*the hamster throws himself onto his back,
*tries to bite and to push the forceps away with his legs
*utters angry shrieks.

25. 
TC are applied either s.c. , i.p. or orally.

Six animals (n=6) are used for each dose.

26. EVALUATION

Stimuli are applied every 20 min for 3 h

Tamed animal selected and checked for coordination

For each dose no. of tamed hamsters and no. of animals
with impaired motor function recorded.

27. 
ED50 values for the taming effect and impairment of
motor function are calculated

neuroleptic width indicates the ratio between the ED
50 for taming and the ED50 for motor disturbances

28. CRITICAL ASSESSMENT OF THE METHOD

neuroleptics can easily be differentiated from sedative and
hypnotic drugs


no training of the animals
no expensive apparatus is needed.

29. 
PURPOSE AND RATIONALE

The cotton rat (Sigmodon hispidus) is a very shy animal which
conceals himself at any time

Innate flight reflex is suppressed by centrally active drugs.

allows the differentiation between neuroleptic and sedative
drugs.

30. PROCEDURE

young animals with a body weight of 40 g are used.

Selective shaving of the fur for identification

At least 6 animals (n=6) divided in two cages are used for
each dose of test compound or Standard

31. 
Fifteen min after application of the drug the test period of 3 h
is started.

The tunnel (cylinder) is lifted and placed to another site

non responders ( to air stream) with the flight reflex it is
considered to be positively influenced

Motor coordination checked

32. EVALUATION

The test procedure is repeated every 15 min over a period of 3
h.

The animals which show
 at least one suppression of the flight reflex during the test
period are counted
 as well as those who slide down on the inclined board.

Using different doses ,ED 50 values are calculated for both
parameters.

33. CRITICAL ASSESSMENT OF THE METHOD

The method allows the differentiation of drugs with
neuroleptic activity against other centrally active drugs.

No training of the animals


no expensive equipment are necessary.

34. PURPOSE AND RATIONALE

Tests effects of reduced
oxygen tension and
cold environment on rats.

The animals are submerged in ice-water the animal, they are
completely anesthetized and immobilized

This kind of artificial hibernation was augmented by
chlorpromazine

35. PROCEDURE

Male Wistar rats weighing 100–150 g

deprived of food with free access to tap water overnight

TC are injected s.c.15 min prior to the start of the experiment.

36. 
At 1 hour, the vessels are opened every 10 min for exactly 10 s

observed for signs of artificial hibernation

An animal is considered positive, when it remains on the
back, even if the extremities are stretched out

37. EVALUATION

Various doses are applied to groups of 10 animals.

Percentage of positive animals is calculated for each group

ED 50 values with confidence limits

38. PURPOSE AND RATIONALE

failure to correct an externally imposed, unusual posture over
a prolonged period of time

APDs which have an inhibitory action on the nigro-striatal
dopamine system induce catalepsy

cataleptic symptoms in rodents have been compared to the
Parkinson-like extra pyramidal side effects

39. PROCEDURE

Groups of 6 male Sprague-Dawley or Wistar rats with a body
weight between 120 and 250 g are used.

They are dosed i.p. with TC or the standard.

Placed individually into translucent plastic boxes

Adaptation time of 2 min

40. 
Amount of time spent with at least 1 forepaw on the bar is
determined

When the animal removes its paws, the time is recorded and
the rat is repositioned on the bar

Three trials are conducted for each animal at 30, 60, 120 and
360 min.

42. EVALUATION

Cataleptic if it remains on the bar for 60 s

% of cataleptic animals is calculated

For DRC, the test is repeated with various doses

ED 50 values can be calculated.

43. CRITICAL ASSESSMENT OF THE METHOD

The phenomenon of catalepsy can be used for measuring the
efficacy

The potential side effects of neuroleptics are evaluted

44. PURPOSE AND RATIONALE

Avoidance escape procedure used to
separate neuroleptics from sedatives and anxiolytics

Sedative compounds suppress both avoidance and escape

Neuroleptic drugs reduce avoidance without affecting
escape

45. PROCEDURE

Male Evans rats 250 g used

Scrambled shock is delivered to the grid floor of the
chamber with 2.8-kHz speaker and a 28-V light on top

Pole suspended from by upper center of the chamber

46. 
Response recorded when rat jumps on the pole and activates
the micro switch

Activation of the light and the speaker together are used as
the conditioning stimulus
-Presented alone for 4 s
-Coincided with the unconditioned stimulus, a
scrambled shock for 26 s

47. 
Pole climb response during the conditioned stimulus is
considered an avoidance response

A response during the time when both the conditioned and
unconditioned stimuli are present is considered an escape
response

Test sessions consist 60 min

48. EVALUATION

Data are expressed in terms
-the number of avoidance and
-escape failures relative to standard

ED 50 values can be calculated using different doses.

49. PURPOSE AND RATIONALE

useful to detect neuroleptics but also
shows positive effects with anxiolytics and other centrally
effective drugs.

fighting behavior seen after lesions in the septal area of the
brain

50. PROCEDURE

Male mice (NMRI), weight between20 and 30 g

A 60-Hz current is delivered for 5s followed by 5 s. intermission
for 3 min.

Each pair of mice is dosed and tested without previous exposure.

The total number of fights are recorded for each pair during the
3-min period.

51. 
The TC or the standard are applied
30 min before the test i.p. or
60 min before the test orally

For a time response,
the drug is given 30, 60 and 120 min prior to testing.

52. 
Six pairs(n=2*6) of drug-treated

two pairs(n=2*2) of vehicle-treated

A dose range is tested at the peak of drug activity

Min. 3 doses (10 pairs of mice/dose) is administered for a
range of doses

Control animals receive the vehicle

53. EVALUATION

The percent inhibition of aggression is calculated from the
vehicle control

ED 50 -values are calculated.

54. CRITICAL ASSESSMENT OF THE METHOD

Not only neuroleptics but also anxiolytics classes of drugs
can be evaluated

Animals required are more(double)

55. PURPOSE AND RATIONALE

Electrical stimulation of selected brain loci
produces effects which are positively
reinforcing and pleasurable

Implantion in the median forebrain bundle at the level of
hypothalamus.

Neuroleptics have been shown to be potent blockers of self
stimulation

56. PROCEDURE

Male Wistar rats (350–400 g) are anesthetized

Heads placed on a level plane in a
stereotactic instrument

electrodes placed at the medium forebrain bundle,

The assembly is then permanently affixed

57. 
10 days for recovery

Animals are trained to bar press in a standard operant box
outfitted with a single lever.

The reward stimulus generated .

The parameters are set at a pulse duration of 0.5 ms with 2.5 ms
between each pulse pair.

58. 
The train of pulses are delivered range from 0.1 to 0.5 mA
using the lowest setting that will sustain maximal responding.

Compounds are administered 60 min prior to testing.

All data are collected on both cumulative recorders and
counters

60. EVALUATION

The number of drug responses are compared to the number of
responses made during each animal’s 30 min control session on
the preceding day

ED 50 values with 95% confidence limits can be calculated.

61. CRITICAL ASSESSMENT OF THE METHOD

Active neuroleptic drugs inhibit the self-stimulation behavior
in very small doses.

The relative potency observed in this test of clinically
efficacious drugs parallels their potency in the treatment of
schizophrenia.

62. 
Amphetamine group toxicity

Inhibition of amphetamine stereotypy in rats

Inhibition of apomorphine climbing in mice

Inhibition of apomorphine stereotypy in rats

Yawning/penile erection syndrome in rats

Inhibition of mouse jumping

63. 
Antagonism against MK-801 induced locomotion and falling
in mice

Inhibition of apomorphine-induced emesis in the dog

Purposeless chewing in rats

Single unit recording of A9 and A10 midbrain
dopaminergic neurons

In vivo voltammetry

64. PURPOSE AND RATIONALE

Mice exhibit an elevated motor activity
after high dose amphetamine ,
increased by aggregation, even
death within 24 h in 80–100% of control animals.


Neuroleptics reduce this death rate
Non-neuroleptic sympatholytics and anxiolytics do not produce
protection

65. PROCEDURE

Ten male mice of the NMRI-strain

Dosed with TC or the standard either orally or IP

Animals placed in glass jars

66. 
30 min after i.p. or 1 h after oral administration

Mice receive 20 mg/kg d-amphetamine s.c.

Mortality is assessed 1, 4 and 24 h after dosing

67. EVALUATION

Mortality of amphetamine only treated animals is at
least 80%

The estimation of ED50 values for protection is
calculated

68. PURPOSE AND RATIONALE

In rats amphetamine induces a characteristic stereotypic
behavior

continuous sniffing, licking or chewing

This behavior prevented by neuroleptic agents

70. 
Animals are observed 60 min after drug administration

An animal is considered to be protected, if the stereotypic
behavior is reduced or abolished

71. PROCEDURE
Group of 6 Wistar rats ,120 -200 g

Simultaneously injected
s.c.amphetamine (10 mg/kg) and
test compound i.p.

.
Placed individually in stainless-steel cages

72. EVALUATION

Percent effectiveness of a drug determined by the number of
animals protected in each group

ED50 values are calculated
Chlorpromazine 1.75 mg/kg i.p
Haloperidol 0.2 mg/kg i.p.

75. CRITICAL ASSESSMENT OF THE METHOD

a simple method to detect neuroleptic activity

may reflect the effects in the corpus striatum
(Parkinsonism-like side effect)

76. PURPOSE AND RATIONALE

Administration of apomorphine to mice results in a peculiar
climbing behavior

Initially rearing and then full-climbing activity,

predominantly mediated by the mesolimbic DA system

APDs Antagonize this behavior with potential

77. PROCEDURE

10 male mice (20–22 g) are treated
i.p. or orally with TC or the vehicle

injected s.c. with 3 mg/kg apomorphine 30 min. later

observed for climbing behavior @ 10, 20 and 30 min

79. 
for climbing behavior , they are scored as
0 = four paws on the floor,
1 = forefeet holding the vertical bars,
2 = four feet holding the bars.

80. EVALUATION

Average values of the drug-treated animals are compared with
those of the controls
(the decrease is expressed as %)

The ED50-values and confidence limits are calculated

82. PURPOSE AND RATIONALE

Apomorphine induces a characteristic stereotyped behavior in
rats,
licking, sniffing and gnawing
in a repetitive, compulsive manner

Compounds which prevent
antagonize DA receptors in the nigrostriatum
predictive for EPS and tardive dyskinesias

84. PROCEDURE

Groups of 6 male Wistar rats 120 and 200 g are used

The TC or the standard are administered i.p. 60 min prior
apomorphine dosage.

Apomorphine HCl is injected s.c. at a dose of 1.5 mg/kg.

85. 
The animals are placed in individual plastic cages

A 10 s observation period 10 min after apomorphine
administration.

An animal is considered protected if this behavior is reduced
or abolished

87. EVALUATION

The % effectiveness of a drug is determined by the number of
animals protected in each group.

With a group size of 10 animals dose response curves are
obtained and ED 50 values calculated.
0.2 mg/kg s.c. for haloperidol and
5.0 mg/kg for chlorpromazine
clozapine was ineffective even at high doses.

89. PURPOSE AND RATIONALE

Yawning occurs alone or associated with stretching and/or
penile erection in humans and in animals

The yawning-penile erection syndrome can be induced in rats
by apomorphine and other DA autoreceptor stimulants

Antagonism against this syndrome can be regarded as
indication of antipsychotic activity

90. PROCEDURE

Naive male Wistar rats, weighing 220–280 g

Rats are pretreated with apomorphine (0.02 to 0.25 mg/kg s.c.)

Rats are placed in individual transparent cages.

Yawning is a fixed innate motor pattern characterized by a
slow, wide opening of the mouth

91. 

Penile erection behaviours are present if
*repeated pelvic thrusts immediately f/b
*an upright position and emerging engorged penis
which the rats proceeds to lick while eating
the ejaculate.
The number of penile erections and yawns is counted for 30
min following the last injection.

93. EVALUATION

The results are expressed as the mean number of yawns and of
penile erections per group

The statistical significance is determined by comparing the
results of each group with the results of the relevant control
group

94. CRITICAL ASSESSMENT OF THE METHOD

yawning and penile erection in rats underlie different
neurochemical mechanisms (Ach)

an useful behavioral tool to study putative antipsychotic
activity of new compounds.

95. PURPOSE AND RATIONALE

The
mouse
jumping
is
due
to
dopaminergic
overstimulation similar to stereotypy

Induced by higher doses of amphetamine

The phenomenon can be blocked by neuroleptics

96. PROCEDURE

Male CD-1 mice 22–25 g

TC injected IP/ Orally

45 mins later 4 mg/kg d-amphetamine sulfate SC

97. 
15 min. later IP injection of 400 mg/kg L-dopa

Mice spontaneously begin to jump at a high rate

Responses after drug administration measured through
pressure-sensitive switch closure or properly positioned
photoelectric beam disruptions

98. EVALUATION

Jumps of mice treated with TC or standard are counted and
expressed as % of jumps in amphetamine group
CRITICAL ASSESSMENT OF THE METHOD

Sensitive and specific for neuroleptic drugs

99. PURPOSE AND RATIONALE

MK-801, a non-competitive NMDA antagonist

Characteristic stereotypy in mice marked by locomotion and
falling behavior

both dopamine dependent and dopamine independent
mechanisms

Antipsychotic agents dose-dependent antagonize this MK-801
induced behavior.

100. PROCEDURE

Male CD-1 mice (20–30 g)

individually placed in activity boxes lined with wire mesh
flooring and allowed to acclimate for 60 min.

dosed with TC 30 min prior to s.c. administration of MK-801
at 0.2 mg/kg

Observed for locomotion and the presence of falling behavior
15 min following MK-801 administration.

101. EVALUATION

ED 50 values and 95% confidence limits are calculated

102. PURPOSE AND RATIONALE

The blockade of centrally acting Da mechanisms

Apomorphine pronounces emetic effect in dogs

Anti-emetic activity and anti-psychotic activity are thought to
be due to dopaminergic blockade

the sites of action are in different brain areas and there is a
lack of complete correlation of these activities.

103. PROCEDURE

Adult beagle dogs of either sex are used in treatment
groups of three to nine dogs/dose.

The dogs are given the TC in a gelatin capsule

then dosed with 0.15 mg/kg apomorphine s.c. at various
intervals after administration of the TC

104. 
observed for overt behavioral effects
pupillary response to light
changes in salivation ,sedation, tremors

Then after apomorphine, the dogs are observed for stereotypic
sniffing, gnawing and the emetic response.

Emesis is defined as wretching movements followed by an
opening of the mouth and either attempted or successful
ejection of stomach content.

105. EVALUATION

minimal effective dose or an ED 50 value for ant-emetic effect

The ED 50 values for
haloperidol 0.06 mg/kg p.o.
chlorpromazine 2.0 mg/kg p.o.

Clozapine was not effective at doses between 2 and 10 mg/kg.
p.o.

106. CRITICAL ASSESSMENT OF THE METHOD

Non-classical neuroleptics like clozapine did not show
pronounced activity the test has been abandoned.

Moreover, tests in higher animals like dogs are limited due to
regional regulations.

107. PURPOSE AND RATIONALE

Chewing can also be induced by chronic administration of
neuroleptics in rats

Purposeless chewing is mediated by dopaminergic and
nicotinic mechanisms.

108. PROCEDURE

Male albino rats are housed 10 per cage

The antagonists e.g. sulpiride or mecamylamine as
standards, are given at different doses 30 min before treatment
either with 0.01 mg/kg nicotine or 1 mg/kg pilocarpine i.p.

Number of chewings are counted by direct observation
immediately after drug administration.

The results are presented as number of chews in a 30 min
period..

109. EVALUATION


Analysis of variance (ANOVA) are used to evaluate the
significance of theresults obtained.
P< 0.05 is considered as significant.

110. PURPOSE AND RATIONALE

Acute treatment with APDs, the number of spontaneously
firing cells is increased in both areas.

After 21 days, ---decrease in the A10neurons,
----APDs with EPS effects induced a decrease A9 cell also

Clozapine caused depolarization inactivation of
A10 neurons but not A9 cells.

112. PROCEDURE

Male Wistar rats weighing 280–360 g are anesthetized

The animal is mounted in a stereotaxic apparatus

twelve separate tracks ( 200 µm apart)in each region

113. 
In an anesthetized rat, a neuron is considered
to be dopaminergic
-triphasic positive-negative-positive spike
-0.4 to 1.5 mV amplitude and 2.5 ms duration
-firing in an irregular pattern of 3 to 9 Hz

114. 
Animals pretreated with vehicle prior to neuronal
sampling serve as controls.

acute single-unit dopamine neuron sampling assay,
TC are administered i.p. 1 hr prior to the beginning of
dopamine neuron sampling.

chronic single-unit dopamine sampling assay,
TC are administered once a day for 21 days
sampling is begun 2 h after the last dose on the 21 st day

115. EVALUATION

Drug treatment groups are compared to vehicle groups with a
one-way ANOVA

116. PURPOSE AND RATIONALE



Electrochemical technique that uses carbon fiber
microelectrodes stereotactically implanted in brain areas
To monitor monoamine metabolism and release
a miniaturized optoelectronic system for telemetry of in vivo
voltammetric signals in freely moving animals

119. PROCEDURE

Electrically pretreated for simultaneous recording of ascorbic
acid DOPAC and 5-HIAA

Male Sprague Dawley rats weighing 270–340 g used

Reference and auxiliary electrodes are positioned on the
surface of the dura

Test electroes placed in the left or right nucleus accumbens
and contralateral anterior striatum,

120. 
Drugs are injected subcutaneously.

Voltammograms are recorded

alternatively from each region every 5 min and after a 1 h
stabilization period.

121. EVALUATION

Voltammetric data are expressed as
% changes from pre-injection control values
( mean of the last 6 peak heights)

Paired Student’s t-test done for significance

122. 








D 1 Receptor assay: [ 3 H]-SCH 23390 binding to rat striatal
homogenates
D 2 Receptor assay: [ 3 H]-spiroperidol binding .
Dopamine D 2 receptor autoradiography ( 3 H-Spiperone
binding)
Binding to the D 3 receptor .
Binding to D 4 receptors
Determination of dopamine autoreceptor activity(hplc)
Dopamine-sensitive adenylate cyclase in rat striatum .
α 1 -adrenergic receptor binding in brain.
[ 3 H]Spiroperidol binding to 5HT 2 receptors in rat cerebral
cortex

123. Serotonin 5HT 2 receptor autoradiography ( 3 H-Spiperone
binding)
 Binding to the sigma receptor
 Simultaneous determination of norepinephrine, dopamine,
DOPAC, HVA, HIAA, and 5-HT from rat brain areas .
 Measurement of neurotransmitters by intracranial
microdialysis
 Use of push-pull cannulae to determine the release of
endogenous neurotransmitters( in vivo)
 Fos protein expression in brain (immunocytochemical)
 Neurotensin receptor binding (endogenous neuroleptic)


124. 
Conditioning stimulus
current relationship with a reinforcer,
past experience with that stimulus

(LI) indexes the deleterious effects of non reinforced stimulus
pre-exposure on the subsequent conditioning to that stimulus.

125. first stage (pre-exposure)
one group >stimulus with no consequences,
second group does not receive the stimulus.
↓
(conditioning)
pre-exposed stimulus reinforcement
↓
previous learning stimulus interferes
with the expression of subsequent learning

126. LATENT INHIBITION MODEL OF
ANTI-PSYCHOTIC DRUG ACTION

LI in an off-baseline conditioned emotional response (CER)
procedure using water licking as the operant response

three stages, different day:
preexposure
conditioning
test

LI consists of the fact that the PE rats show a significantly
lower suppression of drinking than their NPE counterparts

127. Procedure

LI procedure rats are trained to lick in the experimental
chambers (baseline)

Pre-exposure and conditioning are conducted 24 h apart
and are given off-baseline

In addition, we interpolate a day of drinking (re-baseline)
between conditioning and test

Drugs are administered in pre-exposure and/or conditioning
only.

128. 
Reversal of Amphetamine-Induced Latent
Inhibition Disruption

Latent Inhibition Potentiation

Dissociation Between Typical and Atypical
Antipsychotic Drugs in the Latent Inhibition Model

129. FST and in the LI procedure with 40 preexposures and
5 conditioning trials

1. Haloperidol increased immobility in the FST and
potentiated LI

2. Clozapine decreased immobility in the FST and
potentiated LI

3. Imipramine decreased immobility in the FST
while having no effect on LI

130. 
provide more precise information (compared to systemic
drug administration) on the site of the damage

conventional hippocampal lesion,
excitotoxic entorhinal cortex lesion
electrolytic shell lesion)



131. Double advantage

Non-pharmacological

consistent with neurodevelopmental hypothesis of
schizophrenia

rats reared in isolation show PPI deficits in adulthood that
are reversed by both typical and atypical APDs

132. 
LI measures a cognitive process

Reflects the operation of analogous processes b/w human &
rats

The model predicts antipsychotic activity for both
typical and atypical APDs

APDs-induced potentiation of LI is specific and
selective for APD

LI model does not rely on pharmacological
means to elicit the behavioral index

133. 
The model has shed light on the mechanism of effect is
mediated via DA blockade in the NAC during conditioning.

LI–FST model indicates that the utility for other disorders too.

LI shows the relationship between the effects of these drugs
and the site of brain damage,