ORIGINAL INVESTIGATION The atypical antipsychotic risperidone reverses the recognition memory deficits induced by post-weaning social isolation in rats Allison L. McIntosh & Theresa M. Ballard & Lucinda J. Steward & Paula M. Moran & Kevin C. F. Fone Received: 28 September 2012 / Accepted: 23 January 2013 # Springer-Verlag Berlin Heidelberg 2013 Abstract Rationale Rearing rats in isolation from weaning is an established preclinical neurodevelopmental model which induces behavioural deficits with apparent translational rel- evance to some core symptoms of schizophrenia. Objective This study evaluated the ability of the atypical antipsychotic risperidone to reverse behavioural deficits in- duced 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 immedi- ately 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 selec- tively reversed the NOD deficit in isolation-reared rats. Risper- idone 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. Keywords Risperidone . Post-weaning social isolation . Schizophrenia . Cognition . Recognition memory Abbreviations ANOVA Analysis of variance CER Conditioned emotional response GABA γ-Aminobutyric acid ITI Inter-trial interval LMA Locomotor activity NOD Novel object discrimination Prh Perirhinal cortex PND Postnatal day PPI Prepulse inhibition SI Socially isolated GH Group-housed Introduction Schizophrenia is a complex multifactorial, neurodevelop- mental disorder which is influenced by genetic and environ- mental factors and presents with positive (hallucinations and This study was financially supported by F. Hoffmann-La Roche Ltd. A. L. McIntosh : K. C. F. Fone (*) School of Biomedical Sciences, Medical School, Queen’ s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK e-mail: kevin.fone@nottingham.ac.uk T. M. Ballard : L. J. Steward F. Hoffmann-La Roche AG, pRED, Pharma Research & Early Development, DTA Neuroscience, Grenzacherstrasse 124, Basel CH4070, Switzerland P. M. Moran School of Psychology, University of Nottingham, University Park, Nottingham NG7 2RD, UK Psychopharmacology DOI 10.1007/s00213-013-3011-2