The atypical antipsychotic risperidone reverses the recognition memory deficits induced by post-weaning social isolation in rats

• Published in: Psychopharmacology 2013-07, Vol.228 (1), p.31-42
• Main Authors: McIntosh, Allison L., Ballard, Theresa M., Steward, Lucinda J., Moran, Paula M., Fone, Kevin C. F.
• Format: Article
• Language: English
• Subjects: Animal cognition; Animal memory; Animals; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - pharmacology; Behavior, Animal - drug effects; Biomedical and Life Sciences; Biomedicine; Conditioning (Psychology) - drug effects; Discrimination Learning - drug effects; Disease Models, Animal; Dosage and administration; Dose-Response Relationship, Drug; Drug interactions; Health aspects; Male; Memory; Memory Disorders - drug therapy; Memory Disorders - etiology; Motor Activity - drug effects; Neurosciences; Original Investigation; Pharmacology/Toxicology; Physiological aspects; Psychiatry; Psychopharmacology; Psychotropic drugs; Rats; Reflex, Startle - drug effects; Risperidone; Risperidone - administration & dosage; Risperidone - pharmacology; Rodents; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - physiopathology; Social Isolation - psychology; Time Factors
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-013-3011-2

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.