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Science 17 March 2000:
Vol. 287. no. 5460, pp. 2020 - 2022
DOI: 10.1126/science.287.5460.2020
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Reports

Reversal of AntipsychoticInduced Working Memory Deficits by Short-Term Dopamine D1 Receptor Stimulation

Stacy A. Castner, Graham V. Williams, Patricia S. Goldman-Rakic *

Chronic blockade of dopamine D2 receptors, a common mechanism of action for antipsychotic drugs, down-regulates D1 receptors in the prefrontal cortex and, as shown here, produces severe impairments in working memory. These deficits were reversed in monkeys by short-term coadministration of a D1 agonist, ABT 431, and this improvement was sustained for more than a year after cessation of D1 treatment. These findings indicate that pharmacological modulation of the D1 signaling pathway can produce long-lasting changes in functional circuits underlying working memory. Resetting this pathway by brief exposure to the agonist may provide a valuable strategy for therapeutic intervention in schizophrenia and other dopamine dysfunctional states.

Section of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
*   To whom correspondence should be addressed. E-mail: Patricia.Goldman-Rakic{at}yale.edu

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