Reversal of antipsychotic-induced working memory deficits by short-term doper D1 receptor stimulation

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 de ficits were reversed in monkeys by short-term coadministration of a D1 agon ist, ABT 431, and this improvement was sustained for more than a year after cessation of D1 treatment. These findings indicate that pharmacological mo dulation of the D1 signaling pathway can produce long-lasting changes in fu nctional circuits underlying working memory. Resetting this pathway by brie f exposure to the agonist may provide a valuable strategy for therapeutic i ntervention in schizophrenia and other dopamine dysfunctional states.