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.
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Acknowledgements
We thank John Chambers for performing brain dissections. REF was supported by a research fellowship from the Ontario Mental Health Foundation. SK is supported by a Canada Research Chair and by a Special Initiative grant from the Ontario Mental Health Foundation.
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Featherstone, R., Rizos, Z., Nobrega, J. et al. Gestational Methylazoxymethanol Acetate Treatment Impairs Select Cognitive Functions: Parallels to Schizophrenia. Neuropsychopharmacol 32, 483–492 (2007). https://doi.org/10.1038/sj.npp.1301223
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DOI: https://doi.org/10.1038/sj.npp.1301223
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