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Chronic clozapine treatment improves the alterations of prepulse inhibition and BDNF mRNA expression in the medial prefrontal cortex that are induced by adolescent social isolation

Li, Mana,b,c,*; Wang, Weiwene,*; Sun, Land; Du, Weid; Zhou, Haod; Shao, Fengd

doi: 10.1097/FBP.0000000000000419
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Isolation rearing produces significant behavioral and neurochemical dysfunctions in rodents, which resemble the symptoms of schizophrenia. Clozapine, one of the atypical antipsychotics, is widely used in the treatment of schizophrenia patients and in experimental studies. In this study, male Sprague Dawley rats were randomly assigned to either group-reared or isolation-reared conditions during postnatal days (PNDs) 21–34. During PNDs 46–55, the rats were subjected to chronic clozapine (1.0 mg/kg for 10 days) or saline treatment. On PND 56, all rats underwent behavioral testing and then were sacrificed for biochemical testing. The results indicated that adolescent social isolation induced impairments in prepulse inhibition and reversal learning, and clozapine injection improved the prepulse inhibition disruption but not reversal learning ability. Furthermore, clozapine administration reversed the increased brain-derived neurotrophic factor (BDNF) mRNA level in the medial prefrontal cortex (mPFC) that was induced by adolescent isolation. However, clozapine decreased the BDNF mRNA level in the mPFC in group-reared rats. Together, our findings provide additional evidence that a low dose of chronic clozapine treatment could improve information filtering/sensorimotor gating and alterations in the BDNF mRNA level in the mPFC induced by adolescent social isolation.

aDepartment of Psychology

bAcademy of Psychology and Behavior, Tianjin Normal University

cCenter of Collaborative Innovation for Assessment and Promotion of Mental Health, Tianjin

dSchool of Psychological and Cognitive Science, Beijing Key Laboratory of Behavior and Mental Health, Peking University

eKey laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China

*Man Li and Weiwen Wang contributed equally to the writing of this article.

Correspondence to Feng Shao, PhD, School of Psychological and Cognitive Science, Beijing Key Laboratory of Behavior and Mental Health, Peking University, 5 Yiheyuan Road, Beijing, 100871, China E-mail: shaof@pku.edu.cn

Received October 31, 2017

Accepted June 22, 2018

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