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

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Abstract

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.

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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

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Acknowledgments

The authors would like to thank Ian Topham and Stacey Knapp for their technical assistance and F. Hoffmann-La Roche Ltd. for their financial support.

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Authors and Affiliations

  1. School of Biomedical Sciences, Medical School, Queen’s Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK

    Allison L. McIntosh & Kevin C. F. Fone

  2. F. Hoffmann-La Roche AG, pRED, Pharma Research & Early Development, DTA Neuroscience, Grenzacherstrasse 124, Basel, CH4070, Switzerland

    Theresa M. Ballard & Lucinda J. Steward

  3. School of Psychology, University of Nottingham, University Park, Nottingham, NG7 2RD, UK

    Paula M. Moran

Authors
  1. Allison L. McIntosh
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  2. Theresa M. Ballard
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  3. Lucinda J. Steward
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  4. Paula M. Moran
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  5. Kevin C. F. Fone
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Corresponding author

Correspondence to Kevin C. F. Fone.

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This study was financially supported by F. Hoffmann-La Roche Ltd.

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McIntosh, A.L., Ballard, T.M., Steward, L.J. et al. The atypical antipsychotic risperidone reverses the recognition memory deficits induced by post-weaning social isolation in rats. Psychopharmacology 228, 31–42 (2013). https://doi.org/10.1007/s00213-013-3011-2

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  • DOI: https://doi.org/10.1007/s00213-013-3011-2

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