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Science 7 May 2004:
Vol. 304. no. 5672, pp. 878 - 880
DOI: 10.1126/science.1094987
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Reports

Cognitive Inflexibility After Prefrontal Serotonin Depletion

H. F. Clarke,1 J. W. Dalley,1 H. S. Crofts,1 T. W. Robbins,1 A. C. Roberts2*

Serotonergic dysregulation within the prefrontal cortex (PFC) is implicated in many neuropsychiatric disorders, but the precise role of serotonin within the PFC is poorly understood. Using a serial discrimination reversal paradigm, we showed that upon reversal, selective serotonin depletion of the marmoset PFC produced perseverative responding to the previously rewarded stimulus without any significant effects on either retention of a discrimination learned preoperatively or acquisition of a novel discrimination postoperatively. These results highlight the importance of prefrontal serotonin in behavioral flexibility and are highly relevant to obsessive-compulsive disorder, schizophrenia, and the cognitive sequelae of drug abuse in which perseveration is prominent.

1 Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge, UK.
2 Department of Anatomy, University of Cambridge, Downing Street, Cambridge, UK.

* To whom correspondence should be addressed. E-mail: acr4{at}cam.ac.uk

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