Global brain volume reductions in a sub-chronic phencyclidine animal model for schizophrenia and their relationship to recognition memory

Nazanin Doostdar, Eugene Kim, Ben Grayson, Michael Harte, Joanna Neill, Anthony C. Vernon

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Abstract

Background: Cognitive deficits and structural brain changes co-occur in patients with schizophrenia. Improving our understanding of the relationship between these is important to develop improved therapeutic strategies. Back-translation of these findings into rodent models for schizophrenia offers a potential means to achieve this goal. Aims: To determine the extent of structural brain changes and how these relate to cognitive behaviour in a sub-chronic phencyclidine (scPCP) rat model. Methods: Performance in the novel object recognition (NOR) task was examined in female Lister Hooded (LH) rats at 1 and 6 weeks after scPCP (2 mg/kg i.p. n=15) and saline controls (1 ml/kg i.p. n=15). Locomotor activity (LMA) following acute PCP challenge was also measured. Brain volume changes were assessed in the same animals using ex vivo structural magnetic resonance imaging (sMRI) and computational neuroanatomical analysis at 6 weeks. Results: Female scPCP treated LH rats spent significantly less time exploring novel objects (p<0.05) at both time points and had significantly greater LMA response to an acute PCP challenge (p<0.01) at 3-4 weeks of washout. At 6 weeks, scPCP treated LH rats displayed significant global brain volume reductions (p<0.05; q<0.05), without apparent regional specificity. Relative volumes of the perirhinal cortex were however positively correlated with novel object exploration time in scPCP rats at this time point. Conclusion: A sustained scPCP-induced cognitive deficit in NOR is accompanied by global brain volume reductions in female LH rats. The relative volumes of the perirhinal cortex however are positively correlated with novel object exploration, indicating some functional relevance.
Original languageEnglish
JournalJournal of Psychopharmacology
Early online date7 May 2019
DOIs
Publication statusE-pub ahead of print - 7 May 2019

Research Beacons, Institutes and Platforms

  • Lydia Becker Institute
  • Manchester Institute for Collaborative Research on Ageing

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