Behavioural alterations in rats following neonatal hypoxia and effects of clozapine: implications for schizophrenia

Fendt, M., Lex, A., Falkai, P., Henn, F. A., Schmitt, A. (July 2008) Behavioural alterations in rats following neonatal hypoxia and effects of clozapine: implications for schizophrenia. Pharmacopsychiatry, 41 (4). pp. 138-45. ISSN 0176-3679 (Print)0176-3679 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/18651342
DOI: 10.1055/s-2008-1058107

Abstract

INTRODUCTION: As a consequence of obstetric complications hypoxia has been discussed as a possible factor in the pathophysiology of schizophrenia. The present study investigated the effects of weak chronic neonatal hypoxia in rats on different behavioural animal models of schizophrenia. METHODS: (1) After neonatal hypoxia, half of the pups were fostered by normally treated nurse animals to control for possible maternal effects. (2) The animals were tested on postnatal days (PD) 36, 86, 120 and 150 by applying three different behavioural tests: prepulse inhibition (PPI), social interaction and recognition, and motor activity in an open field. (3) Before the PD 150 test, half of the animals had been chronically treated with the antipsychotic drug clozapine (45 mg/kg/day). RESULTS: Rats exposed to hypoxia as neonates exhibited a deficit in locomotor activity on PD 86, 120, and 150, as well as a PPI deficit on PD 120 and 150 but not before. Chronic treatment with clozapine reverses the hypoxia induced PPI deficit, but not the decreased locomotor activity. In a second experiment, clozapine was chronically administered before PD 120 and blocked the development of the PPI deficit in the animals exposed to hypoxia. DISCUSSION: The time course of the hypoxia-induced PPI deficit and reversibility by clozapine supports the validity of our animal model and the hypothesis that hypoxia as an obstetric complication is an important factor in the pathophysiology of schizophrenia.

Item Type: Paper
Uncontrolled Keywords: Acoustic Stimulation Age Factors Animals Animals, Newborn Anoxia/ drug therapy Antipsychotic Agents/ therapeutic use Behavior, Animal/ drug effects Clozapine/ therapeutic use Disease Models, Animal Inhibition (Psychology) Interpersonal Relations Motor Activity/drug effects Rats Rats, Sprague-Dawley Startle Reaction/drug effects/physiology
Subjects: diseases & disorders
diseases & disorders > mental disorders
diseases & disorders > mental disorders > schizophrenia
organism description > animal
organism description > animal behavior
organism description > animal > developmental stage > child
organs, tissues, organelles, cell types and functions > organelles, types and functions > hypoxia
organs, tissues, organelles, cell types and functions > organelles, types and functions
organs, tissues, organelles, cell types and functions
organism description > animal > mammal > rodent > rat
organism description > animal > mammal > rodent > rat
CSHL Authors:
Communities: CSHL labs > Henn lab
Depositing User: Matt Covey
Date: July 2008
Date Deposited: 28 Feb 2013 15:38
Last Modified: 28 Feb 2013 15:38
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27493

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