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Science 15 August 1997:
Vol. 277. no. 5328, pp. 953 - 955
DOI: 10.1126/science.277.5328.953
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Reports

Enduring Cognitive Deficits and Cortical Dopamine Dysfunction in Monkeys After Long-Term Administration of Phencyclidine

J. David Jentsch, D. Eugene Redmond Jr., John D. Elsworth, Jane R. Taylor, Kenneth D. Youngren, Robert H. Roth *

The effects of the psychotomimetic drug phencyclidine on the neurochemistry and function of the prefrontal cortex in vervet monkeys were investigated. Monkeys treated with phencyclidine twice a day for 14 days displayed performance deficits on a task that was sensitive to prefrontal cortex function; the deficits were ameliorated by the atypical antipsychotic drug clozapine. Repeated exposure to phencyclidine caused a reduction in both basal and evoked dopamine utilization in the dorsolateral prefrontal cortex, a brain region that has long been associated with cognitive function. Behavioral deficits and decreased dopamine utilization remained after phencyclidine treatment was stopped, an indication that these effects were not simply due to direct drug effects. The data suggest that repeated administration of phencyclidine in monkeys may be useful for studying psychiatric disorders associated with cognitive dysfunction and dopamine hypofunction in the prefrontal cortex, particularly schizophrenia.

J. D. Jentsch, Section of Neurobiology, Yale University School of Medicine, New Haven, CT, USA.
D. E. Redmond Jr., Departments of Psychiatry and Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
J. D. Elsworth and R. H. Roth, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT, USA.
J. R. Taylor, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
K. D. Youngren, Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT, USA.
*   To whom correspondence should be addressed.

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