Gestational methylazoxymethanol acetate treatment impairs select cognitive functions: Parallels to schizophrenia

Abstract

Gestational methylazoxymethanol acetate (MAM) exposure has been suggested to produce neural and behavioral abnormalities similar to those seen in schizophrenia. In order to assess MAM treatment as a model of schizophrenia, pregnant female rats were injected with MAM (22 mg/kg) on gestational day 17 and their offspring were assessed in adulthood on a series of cognitive tasks. The first experiment involved an attentional set-shifting task, a rodent analog of the Wisconsin card sort task. In experiment 2, animals were tested on the 5-choice serial reaction time task, a rodent analog of the continuous performance task. In the final experiment animals were assessed on a differential reinforcement of low rate of responding 20 s schedule of reinforcement (DRL-20), a task that is sensitive to changes in inhibitory control. In the first experiment, MAM-treated animals required a greater number of trials than controls to successfully learn an extradimensional shift on the set-shifting task, and had difficulties in learning to reverse a previously acquired discrimination. In contrast, MAM-treated animals showed little impairment on the 5-choice task, aside from a modest but consistent increase in premature responding. Finally, MAM exposed animals showed substantial impairments in DRL performance. Post-mortem analysis of brain tissue showed significant decreases in tissue weight in the hippocampus, parietal cortex, prefrontal cortex, and dorsal striatum of MAM-treated animals. These results support the notion that MAM treatment may simulate some aspects of schizophrenic cognition. © 2007 Nature Publishing Group. All rights reserved.