Effects'of'risperidone'on'social'and'memory'deficits'in'an'animal'model'of'autism

Habash,'M ,'Presti0Torres,'J ,'Cayer,'C ,'Kent,'P ,'Merali,'Z

1,2 2 2 1,2 1,2
1University'of'Ottawa,'2Institute'of'Mental'Health'Research

INTRODUCTION RESULTS
Autism'Spectrum'Disorders' (ASD)
Symptoms'associated'with'ASD'include'deficits'in'social'interaction'and'memory'retention.
There'is'evidence'that'antipsychotic'medications'may'alleviate'these'deficits'observed' in'psychiatric' SOCIAL'INTERACTION NOVEL'OBJECT'RECOGNITION
disorders.
Since'similar'deficits'are'observed' in'ASD,'antipsychotics'may'provide'a'similar'reversal'effect' in'the' Figure'3.'The'recognition'index'
autism'model. 5'min'Test'1' (TN/(TN+TF))'for'the'control'
group'(vehicle)'vs.'the'RC03095'
RCF3095
(Acute'Treatment) treated'group,'when'given'
RC03095'is'a'selective'gastrin0releasing'peptide'receptor'(GRPr)'antagonist. * either'the'placebo'(sweet'and'
Blocking'GRPr in'neonatal'rats'produces'symptoms'similar'to'those'observed' in'ASD. Figure'1.'Total'time'spent'engaging'in'social'
condensed'milk)'or'risperidone'
The'RC03095'model'could'be'used'to'test'for'a'therapy'to'alleviate'the'behavioural'symptoms'of'ASD. interaction'for'the'control'group'(vehicle)'vs.'the'
for'chronic'daily'doses'from'PD'
RC03095'treated'group,'when'given'either'the'
52'to'PD'60.'Tests'were'done'
Risperidone placebo'(sweet'and'condensed'milk)'or'
on'PD'60.'Data'expressed'as'a'
Risperidone (an'antipsychotic),'which'blocks'mainly'the'serotonin'receptors'at'low'doses'and'the' risperidone'acutely.'Treatments'were'given'on'
mean' SEM.
dopamine'receptors'at'higher'doses,'was'found'to'reverse' social'deficits. PD'35'and'tests'were'done'1.5'hours'later.'Data'
Risperidone may'therefore' be'effective' at'reversing'the'social'and'memory'deficits'observed' in'rats' expressed'as'a'mean' SEM.'*'Significantly'
No'significant'results'were'
treated'neonatally with'RC03095. different'from'control'at'p'<'0.05.'
observed.'The'effects'of'RCF
3095'were'not'exhibited'in'
Rats'treated'neonatally'with'RCF3095'spent'
OBJECTIVES significantly'less'time'engaging'in'social'
adulthood,'and'therefore'
conclusions'about'
interaction'to'the'vehicleFtreated'control'
risperidone'could'not'be'
group,'an'effect'not'observed'when'the'RCF
The'main'objective'of'this'study'is'to'test'the'atypical'antipsychotic,'risperidone,' in'an'animal'model' made.
of'social'and'cognitive'dysfunction. 3095'rats'received'an'injection'of'risperidone.

Does'the'RC03095'model'produce'social'and'memory'deficits'in'rats?
Does'risperidone reverse' these'social'and'memory'deficits'in'the'RC03095'autism'model? 15'min'Test'2'
Is'there'a'difference' between'an'acute'and'chronic'treatment'of'risperidone on'the'social'and/or'
cognitive'deficits? (Chronic'Treatment)
Figure'2.'Total'time'spent'engaging'in'social'
METHODS interaction'for'the'control'group'(vehicle)'vs.'the'
RC03095'treated'group,'when'given'either'the'
placebo'(sweet'and'condensed'milk)'or'
ANIMALS risperidone'for'two'weeks'of'daily'doses'from'PD'
Male'Sprague0Dawley (n=40)'rats'were'bred'in0house'and'received' daily' 52'to'PD'65.'Tests'were'done'on'PD'65.'Data'
injections'of'either'vehicle'(n=20)'or'RC03095'(n=20)'from'postnatal'days'(PD)' expressed'as'a'mean' SEM.
1010.'All'pups'were'weaned'on'PD'21'and'housed'in'pairs'with'a'cage0mate'
that'came'from'the'same'experimental'condition. No'significant'results'were'observed.'The'
Rats'had'free'access'to'food'and'water. effects'of'RCF3095'were'not'exhibited'in' Figure'4.'Social'Interaction'test.'Two'rats'were' Figure'5.'Novel'Object'Recognition'test.'Each'rat'
The'Canadian'Council'on'Animal'Care'and'the'National'Institutes'of'Health' adulthood,'and'therefore'conclusions'about' placed'into'the'square'Plexiglas'arena'(60'x'60' was'placed'into'the'Plexiglas'arena'and'the'time'
guide'for'the'care'and'use'of'Laboratory'animals'was'used'for'all' cm;'30'cm'high'walls),'and'were'allowed'to' spent'sniffing,' touching' and'licking' the'Plastic'
risperidone'could'not'be'made.
experimental'procedures. freely'interact'with'one'another.' Duplo' Lego'toys'(10'cm'tall)'was'observed.

PD'1F10 PD'35 1.5'hours'later PD'52

PD'60
RCF3095
5'min
Novel'Object
RCF3095
Sweet'and'
condensed'
5'min'Social'
Recognition DISCUSSION
milk
Test
Interaction 2'weeks'of'
daily'doses
Test'1 PD'65
Vehicle
15'min'Social' Treating'neonatal'rats'with'the'selective'gastrin0releasing'peptide'receptor'(GRPr)'antagonist,'RC03095,'significantly'
Interaction lowered'social'interaction'at'PD'35,'confirming'the'RC03095'animal'model'of'autism.
Vehicle Test'2
This'effect'was'not'exhibited'when'the'rats'were'adults'at'PD'65.'
It'is'possible'that'the'chronic'treatment'of'sweet'and'condensed'milk/'risperidone'interfered'with'the'results.
SOCIAL'INTERACTION'TEST NOVEL'OBJECT'RECOGNITION'TEST It'is'possible'that'the'effects'of'neonatal'RC03095'do'not'last'until'adulthood.
The'total'time'spent'following,'sniffing,'crawling' Rats'explored'a'square'arena'for'5'min'in'the'presence'
An'acute'treatment'of'risperidone'at'PD'35'partially'reversed'the'social'deficits'exhibited'in'the'RC03095'treated'rats.
over'or'grooming'any'part'of'the'body'of'the'
test'partner'(allogrooming)'were'measured'
of'two'similar'objects'(A;'trial'1)'and'then'a'now'
familiar'object'(A)'and'a'novel'object'(B;'trial'2).
Conclusions'cannot'be'made'about'the'effectiveness'of'chronic'risperidone'on'adulthood'social'and'memory'deficits,'
blindly'by'an'experimenter. Object'exploration'was'measured'blindly'by'an'
experimenter'by'recording'the'time'spent'sniffing,'
as'there'were'no'significant'differences'between'the'control'and'RC03095'groups.
touching'and'licking'both'objects'(A'&'B)'during'trial'2.