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Updated: May 14, 2026
Operant Procedures for Assessing Behavioral Flexibility in Rats
Published on: February 15, 2015
The atypical antipsychotic risperidone reverses the recognition memory deficits induced by post-weaning social
Allison L McIntosh1, Theresa M Ballard, Lucinda J Steward
1School of Biomedical Sciences, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK.
Rationale:
Rearing rats in isolation from weaning is an established preclinical neurodevelopmental model which induces behavioural deficits with apparent translational relevance to some core symptoms of schizophrenia.
Objective:
This study evaluated the ability of the atypical antipsychotic risperidone to reverse behavioural deficits induced by post-weaning social isolation of rat pups and to further characterise the predictive validity of this model.
Method:
Forty-five male Lister hooded rats were housed in groups of 3-4 (n = 16) or singly (n = 29) for 4 weeks immediately after weaning on postnatal day (PND) 22-24. On PND 51, novel cage-induced locomotor activity (LMA) was assessed to subdivide rats into groups balanced for behavioural response. On PNDs 58, 59, 65 and 72, rats received either vehicle (1 ml/kg; i.p.) or risperidone (0.2 or 0.5 mg/kg; i.p.) 30 min prior to testing in LMA, novel object discrimination (NOD), prepulse inhibition (PPI) of acoustic startle and conditioned emotional response (CER) learning paradigms, respectively.
Results:
Isolation rearing had no effect on PPI, but produced LMA hyperactivity and impaired NOD and CER compared to group-housed controls. Risperidone caused a dose-dependent reduction in LMA, irrespective of rearing condition, but selectively reversed the NOD deficit in isolation-reared rats. Risperidone did not reverse the isolation rearing-induced CER deficit.
Conclusions:
Similar to its clinical profile, risperidone only partially reverses the schizophrenic symptomology; since it reversed some, but not all, of the learning and memory deficits induced by post-weaning isolation, the isolation rearing model may be useful to predict antipsychotic activity of novel therapeutic agents.
