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Original Research ARTICLE

Effects of subchronic phencyclidine (PCP) treatment on social behaviors, and operant discrimination and reversal learning in C57BL/6J mice

1
Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcoholism and Alcohol Abuse, NIH, Rockville, MD, USA
2
Department of Experimental Psychology, University of Cambridge, Cambridge, UK
3
Medical Research Council and Wellcome Trust Behavioral and Clinical Neuroscience Institute, Cambridge, UK
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 × 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:
glutamate, mouse, schizophrenia, executive function, negative symptoms, NMDA, psychosis, prefrontal cortex
Citation:
Brigman JL, Ihne J, Saksida LM, Bussey TJ and Holmes A (2009). Effects of subchronic phencyclidine (PCP) treatment on social behaviors and operant discrimination and reversal learning in C57BL/6J mice. Front. Behav. Neurosci. 3:2. doi: 10.3389/neuro.08.002.2009
Received:
19 December 2008;
 Paper pending published:
23 December 2008;
Accepted:
22 January 2009;
 Published online:
23 February 2009.

Edited by:

Jacqueline N. Crawley, National Institute of Mental Health, USA

Reviewed by:

Edward S. Brodkin, University of Pennsylvania School of Medicine, USA
Jacqueline N. Crawley, National Institute of Mental Health, USA
Copyright:
© 2009 Brigman, Ihne, Saksida, Bussey and Holmes. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
*Correspondence:
Jonathan Brigman, Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, 5625 Fishers Lane, Room 2N09, Rockville, MD 20852-9411, USA. e-mail: brigmanj@mail.nih.gov

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