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Clozapine administration in adolescence prevents postpubertal emergence of brain structural pathology in an animal model of schizophrenia

Piontkewitz, Yael, Assaf, Yaniv and Weiner, Ina 2009. Clozapine administration in adolescence prevents postpubertal emergence of brain structural pathology in an animal model of schizophrenia. Biological psychiatry 66 (11) , pp. 1038-1046. 10.1016/j.biopsych.2009.07.005

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Background Schizophrenia is a neuropsychiatric disorder of a neurodevelopmental origin manifested symptomatically after puberty. Structural neuroimaging studies show that neuroanatomical aberrations occur before onset of symptoms, raising a question of whether schizophrenia can be prevented. Treatment with atypical antipsychotic drugs before the development of the full clinical phenotype might reduce the risk of transition to psychosis, but it remains unknown whether neuroanatomical abnormalities can be prevented. We used a neurodevelopmental animal model of schizophrenia to assess the efficacy of the atypical antipsychotic clozapine to prevent neuroanatomical deterioration. Methods Pregnant rats received injection on gestational day 15 with the viral mimic polyriboinosinic-polyribocytidylic acid (PolyI:C) or saline. Structural brain changes in the male offspring were assessed at adolescence and adulthood (35 days and 120 days) with structural neuroimaging. In the second part, male offspring of PolyI:C- and saline-treated dams received daily clozapine (7.5 mg/kg) or saline injection in adolescence (days 34–47) and underwent behavioral testing and imaging at adulthood (from 90 days onward). Results In utero exposure to maternal infection led in the offspring to postpubertal emergence of hallmark structural abnormalities associated with schizophrenia, enlarged ventricles, and smaller hippocampus. These abnormalities were not observed in the offspring of mothers who received PolyI:C that were treated with clozapine in adolescence. This was paralleled by prevention of behavioral abnormalities phenotypic of schizophrenia, attentional deficit, and hypersensitivity to amphetamine. Conclusions This is the first demonstration that pharmacological intervention during adolescence can prevent the emergence of brain structural changes resulting from in-utero insult.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: Elsevier
ISSN: 0006-3223
Last Modified: 21 Aug 2019 02:21

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