Noise stress impairs prefrontal cortical cognitive function in monkeys - Evidence for a hyperdopaminergic mechanism
Noise stress impairs prefrontal cortical cognitive function in monkeys - Evidence for a hyperdopaminergic mechanism
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DOI：
10.1001/archpsyc.55.4.362
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发表时间：
1998-04-01
影响因子：
--
通讯作者：
Goldman-Rakic, PS
中科院分区：
文献类型：
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作者：
Arnsten, AFT;Goldman-Rakic, PS
背景：压力可以加重许多精神疾病，其中许多与前额叶皮质（PFC）认知缺陷有关。生化研究表明，轻度应激优先增加PFC中的多巴胺周转。我们的研究探讨了急性轻度应激暴露对猴子更高认知功能的影响以及多巴胺能机制在应激反应中的作用。方法：在空间工作记忆任务中，研究了大声（105 dB）噪声应激的影响（延迟反应）依赖于PFC，并在参考记忆任务与类似的运动和动机的要求（视觉模式的歧视）依赖于下颞叶皮层。多巴胺机制的作用进行了测试，通过挑战的压力反应与代理，减少多巴胺受体stimulation.Results：暴露于噪声压力显着损害延迟响应性能。压力没有损害性能的“0秒”延迟控制试验，并没有改变视觉模式的歧视性能，这是符合受损的PFC认知功能，而不是非特异性的性能变化。预处理药物，阻断多巴胺受体（氟哌啶醇，SCH 23390）或减少应激诱导的PFC多巴胺周转率在啮齿动物（可乐定，盐酸纳洛酮）。结论：这些结果表明，压力损害PFC认知功能通过高多巴胺能机制。压力可能会使PFC“离线”，以允许更多的习惯性反应，由后部皮质和皮质下结构来调节行为。这种机制可能具有生存价值，但在人类社会中可能经常不适应，导致PFC在许多神经精神疾病中的脆弱性。
Background: Stress can exacerbate a number of psychiatric disorders, many of which are associated with prefrontal cortical (PFC) cognitive deficits. Biochemical studies demonstrate that mild stress preferentially increases dopamine turnover in the PFC. Our study examined the effects of acute, mild stress exposure on higher cognitive function in monkeys and the role of dopaminergic mechanisms in the stress response.Methods: The effects of loud (105-dB) noise stress were examined on a spatial working memory task (delayed response) dependent on the PFC, and on a reference memory task with similar motor and motivational demands (visual pattern discrimination) dependent on the inferior temporal cortex. The role of dopamine mechanisms was tested by challenging the stress response with agents that decrease dopamine receptor stimulation.Results: Exposure to noise stress significantly impaired delayed-response performance. Stress did not impair performance on "0-second" delay control trials and did not alter visual pattern discrimination performance, which is consistent with impaired PFC cognitive function rather than nonspecific changes in performance. Stress-induced deficits in delayed-response performance were ameliorated by pretreatment with drugs that block dopamine receptors (haloperidol, SCH 23390) or reduce stress-induced PFC dopamine turnover in rodents (clonidine, naloxone hydrochloride).Conclusions: These results indicate that stress impairs PFC cognitive function through a hyperdopaminergic mechanism. Stress may take the PFC "off-line" to allow more habitual responses mediated by posterior cortical and subcortical structures to regulate behavior. This mechanism may have survival value, but may often be maladaptive in human society, contributing to the vulnerability of the PFC in many neuropsychiatric disorders.