1. ¹Section of Biopsychology, Centre for Addiction and Mental Health, Toronto, ON, Canada
2. ²Department of Psychiatry, University of Toronto, Toronto, ON, Canada
3. ³Department of Psychology, University of Toronto, Toronto, ON, Canada
4. ⁴Neuroimaging Research Section, Centre for Addiction and Mental Health, Toronto, ON, Canada
5. ⁵Schizophrenia/PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada

Correspondence: Dr RE Featherstone, Section of Biopsychology, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada M5T 1R8, Tel: +1 416 535 8501 (ext 6242), Fax: +1 416 979 6942; E-mail: Rob_Featherstone@camh.net

Received 21 March 2006; Revised 14 June 2006; Accepted 12 July 2006; Published online 11 October 2006.

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.