title: 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.
authors.affiliation: Section of Biopsychology, Centre for Addiction and Mental Health, Toronto, ON, Canada. Rob_Featherstone@camh.net
authors.forename: Robert E
authors.initials: RE
authors.lastname: Featherstone
authors.forename: Zoe
authors.initials: Z
authors.lastname: Rizos
authors.forename: José N
authors.initials: JN
authors.lastname: Nobrega
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fletcher
mesh_terms: D000818:Animals; D001284:Atrophy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001925:Brain Damage, Chronic / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D007859:Learning Disabilities / Q000139:chemically induced / Q000503:physiopathology / Q000523:psychology; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives* / Q000633:toxicity; D009483:Neuropsychological Tests; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012054:Reinforcement, Psychology; D012559:Schizophrenia / Q000209:etiology*; D013723:Teratogens / Q000633:toxicity
chemical_list: D013723:Teratogens; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol