Reversal of antipsychotic-induced working memory deficits by short-term doper D1 receptor stimulation
Reversal of antipsychotic-induced working memory deficits by short-term doper D1 receptor stimulation
复制标题
DOI：
10.1126/science.287.5460.2020
复制
发表时间：
2000-03-17
期刊：
影响因子：
56.9
通讯作者：
Goldman-Rakic, PS
中科院分区：
文献类型：
--
作者：
Castner, SA;Williams, GV;Goldman-Rakic, PS
慢性阻断多巴胺D2受体是抗精神病药物的一种常见作用机制，它会下调前额叶皮层的D1受体，如图所示，会导致工作记忆严重受损。这些缺陷在短期联合给予D1激动剂abt431的猴子中得到逆转，并且这种改善在D1治疗停止后持续一年多。这些发现表明，D1信号通路的药理调节可以在工作记忆的功能回路中产生持久的变化。通过短暂暴露于激动剂来重置这一途径可能为精神分裂症和其他多巴胺功能失调状态的治疗干预提供有价值的策略。
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.