Subchronic treatment with the psychotomimetic phencyclidine (PCP) has been proposed as a rodent model of the negative and cognitive/executive symptoms of schizophrenia. There has, however, been a paucity of studies on this model in mice, despite the growing use of the mouse as a subject in genetic and molecular studies of schizophrenia. In the present study, we evaluated the effects of subchronic PCP treatment (5 mg/kg twice daily x 7 days, followed by 7 days withdrawal) in C57BL/6J mice on (1) social behaviors using a sociability/social novelty-preference paradigm, and (2) pairwise visual discrimination and reversal learning using a touchscreen-based operant system. Results showed that mice subchronically treated with PCP made more visits to (but did not spend more time with) a social stimulus relative to an inanimate one, and made more visits and spent more time investigating a novel social stimulus over a familiar one. Subchronic PCP treatment did not significantly affect behavior in either the discrimination or reversal learning tasks. These data encourage further analysis of the potential utility of mouse subchronic PCP treatment for modeling the social withdrawal component of schizophrenia. They also indicate that the treatment regimen employed was insufficient to impair our measures of discrimination and reversal learning in the C57BL/6J strain. Further work will be needed to identify alternative methods (e.g., repeated cycles of subchronic PCP treatment, use of different mouse strains) that reliably produce discrimination and/or reversal impairment, as well as other cognitive/executive measures that are sensitive to chronic PCP treatment in mice.
Keywords: NMDA; executive function; glutamate; mouse; negative symptoms; prefrontal cortex; psychosis; schizophrenia.