Reversal of antipsychotic-induced working memory deficits by short-term dopamine D1 receptor stimulation |
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| Authors: | Castner S A Williams G V Goldman-Rakic P S |
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| Institution: | Section of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA. |
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| Abstract: | 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. |
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