Journal
NEUROPHARMACOLOGY
Volume 62, Issue 3, Pages 1299-1307Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2011.02.022
Keywords
Set-shifting; Reversal learning; Operant conditioning; PolyI:C; Schizophrenia; Medial prefrontal cortex
Categories
Funding
- National Alliance for Research on Schizophrenia and Depression
- Saskatchewan Health Research Foundation
- University of Saskatchewan Molstad Trust
- National Sciences and Engineering Research Council of Canada
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Current understanding of the etiology of neurodevelopmental disorders is limited; however, recent epidemiological studies demonstrate a strong correlation between prenatal infection during pregnancy and the development of schizophrenia in adult offspring. In particular, schizophrenia patients subjected to prenatal infection exhibit impairments in executive functions greater than schizophrenia patients not exposed to an infection while in utero. Acute prenatal treatment of rodents with the viral mimetic polyinosinic-polycytidylic acid (PolyI:C) induces behavioural and neuropathological alterations in the adult offspring similar to schizophrenia. However, impairments on tasks of executive function that involve the prefrontal cortex (PFC) have been rarely examined for the prenatal infection model. Hence, we investigated the effects of acute prenatal injection of PolyI:C (4.0 mg/kg, i.v., gestational day 15) on strategy set-shifting and reversal learning in an operant-based task. Our results show male, but not female, PolyI:C-treated adult offspring require more trials to reach criterion and perseverate during set-shifting. An opposite pattern was seen on the reversal day where the PolyI:C-treated male rats made fewer regressive errors. Females took more pre-training days and were slower to respond during the trials when compared to males regardless of prenatal treatment. The present findings validate the utility of the prenatal infection model for examining alterations of executive function, one of the most prominent cognitive symptoms of schizophrenia. This article is part of a Special Issue entitled 'Schizophrenia'. (C) 2011 Elsevier Ltd. All rights reserved.
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