Muscarinic and nicotinic receptors synergistically modulate working memory and attention in humans
Muscarinic and nicotinic receptors synergistically modulate working memory and attention in humans
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DOI：
10.1017/s1461145705005407
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发表时间：
2006-04-01
影响因子：
4.8
通讯作者：
Nathan, PJ
中科院分区：
文献类型：
--
作者：
Ellis, JR;Ellis, KA;Nathan, PJ
毒蕈碱和尼古丁受体的功能异常与包括阿尔茨海默病和精神分裂症在内的许多疾病有关。虽然毒蕈碱受体在调节认知中的作用在人类中已得到充分证实，但烟碱受体的作用以及毒蕈碱受体和烟碱受体之间的相互作用和可能的协同作用尚未在人类中得到充分表征。当前的研究检查了选择性和同时的毒蕈碱和烟碱受体拮抗剂对一系列认知过程的影响。该研究是一项双盲、安慰剂对照、重复测量设计，其中12名健康的年轻志愿者在四种急性治疗条件下完成认知测试：安慰剂（P）;美加明（15 mg）（M）;东莨菪碱（0.4 mg i.m.）(S);美加明（15 mg）/东莨菪碱（0.4 mg i.m.）（MS）。东莨菪碱拮抗毒蕈碱受体可导致工作记忆、陈述记忆、持续视觉注意和精神速度的下降。尼古丁拮抗与美加明没有任何影响的认知过程中检查。同时拮抗毒蕈碱和烟碱受体与美卡拉明和东莨菪碱损害东莨菪碱损害的所有认知过程，并产生更大的赤字比单独的毒蕈碱或烟碱阻滞，特别是在工作记忆，视觉注意和精神速度。这些研究结果表明，毒蕈碱和烟碱受体可能在功能上相互作用，特别是对工作记忆和注意力有协同作用，并表明针对两种受体系统的治疗策略可能有助于改善许多疾病的选择性认知过程。
Functional abnormalities in muscarinic and nicotinic receptors are associated With a number of disorders including Alzheimer's disease and schizophrenia. While the contribution of muscarinic receptors in modulating cognition is well established in humans, the effects of nicotinic receptors and the interactions and possible synergistic effects between muscarinic and nicotinic receptors have not been well characterized in humans. The Current Study examined the effects of selective and simultaneous muscarinic and nicotinic receptor antagonism on a range of cognitive processes. The study was a double-blind, placebo-controlled, repeated measures design in which 12 healthy, young volunteers completed cognitive testing under four acute treatment conditions: placebo (P); mecamylamine (15 mg) (M); scopolamine (0.4 mg i.m.) (S); mecamylamine (15 mg)/scopolamine (0.4 mg i.m.) (MS). Muscarinic receptor antagonism with scopolamine resulted in deficits in working memory, declarative memory, Sustained visual attention and psychomotor speed. Nicotinic antagonism with mecamylamine had no effect on any of the cognitive processes examined. Simultaneous antagonism of both muscarinic and nicotinic receptors with mecamylamine and scopolamine impaired all cognitive processes impaired by scopolamine and produced greater deficits than either muscarinic or nicotinic blockade alone, Particularly on working memory, Visual attention and psychomotor speed. These findings suggest that muscarinic and nicotinic receptors may interact functionally to have synergistic effects particularly on working memory and attention and suggests that therapeutic strategies targeting both receptor systems may be useful in improving selective cognitive processes in a number of disorders.