, Volume 228, Issue 1, pp 31–42 | Cite as

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
Original Investigation



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.


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.


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.


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.


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.


Risperidone Post-weaning social isolation Schizophrenia Cognition Recognition memory 



Analysis of variance


Conditioned emotional response


γ-Aminobutyric acid


Inter-trial interval


Locomotor activity


Novel object discrimination


Perirhinal cortex


Postnatal day


Prepulse inhibition


Socially isolated




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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Allison L. McIntosh
    • 1
  • Theresa M. Ballard
    • 2
  • Lucinda J. Steward
    • 2
  • Paula M. Moran
    • 3
  • Kevin C. F. Fone
    • 1
  1. 1.School of Biomedical SciencesMedical School, Queen’s Medical Centre, University of NottinghamNottinghamUK
  2. 2.F. Hoffmann-La Roche AG, pRED, Pharma Research & Early Development, DTA NeuroscienceBaselSwitzerland
  3. 3.School of PsychologyUniversity of Nottingham, University ParkNottinghamUK

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