Dopaminergic modulation of behavioral states in mesopontine tegmentum: A reverse microdialysis study in freely moving cats

Dopaminergic modulation of behavioral states in mesopontine tegmentum: A reverse microdialysis study in freely moving cats
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DOI:
10.1093/sleep/26.7.801
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发表时间:
2003-11-01
期刊:
影响因子:
5.6
通讯作者:
Sakai, K
Sakai, K
中科院分区:
医学2区
文献类型:
--
作者:
Crochet, S;Sakai, K

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研究目的:我们研究了多巴胺(DA)在行为状态控制中的作用,特别是,(或快速眼动)睡眠(PS)的生成在中桥脑结构。设计:反向微透析和多导记录在自由移动的猫被用来评估应用DA和单胺能激动剂和拮抗剂对睡眠-觉醒状态的影响。设置:NAPatients或参与者:NA干预:NA测量和结果:行为状态和脑电图的定量和定性分析表明,DA没有显着的影响时,应用于任何部分的中桥脑被盖,除了周围的蓝斑α,一个区域位于腹内侧的蓝斑,部分α,并严重牵连PS的产生。在此结构中,DA对PS产生选择性的、剂量依赖性的抑制作用,并诱导PS无张力。SKF-81297(一种选择性D-1样激动剂)或选择性D-2样激动剂(如喹喏烷、喹吡罗和7-OH-DPAT)不能模拟这些作用。相反,D-2-样激动剂诱导觉醒显着减少和增加慢波睡眠和PS。然而,DA的作用被应用可乐定(一种选择性α(2)肾上腺素受体激动剂)模拟,并被共同应用RX 821002(一种选择性α(2)肾上腺素受体拮抗剂)阻断。我们的结果表明,DA通过兴奋α(2)肾上腺素受体抑制蓝斑周围α区的PS,但在同一区域应用D-2样激动剂可显著降低觉醒,增加慢波睡眠和PS。这种效应可能是抗帕金森病多巴胺能药物引起的白天过度嗜睡和睡眠发作的原因。
Study Objectives: We investigated the role of dopamine (DA) in behavioral state control and, in particular, paradoxical (or rapid eye movement) sleep (PS) generation in mesopontine structures.Design: Reverse microdialysis and polygraphic recordings in freely moving cats were used to assess the effects on sleep-wake states of applied DA and monoaminergic agonists and antagonists.Settings: NAPatients Or Participants: NAIntervention: NAMeasurements and Results: Quantitative and qualitative analysis of behavioral states and electroencephalogram showed that DA had no significant effect when applied to any part of the mesopontine tegmentum, except the peri-locus coeruleus alpha, a region located just ventromedial to the locus coeruleus, pars alpha, and critically implicated in PS generation. In this structure, DA caused a selective and dose-dependent inhibition of PS and induced PS without atonia. These effects were not mimicked by SKF-81297, a selective D-1-like agonist, or selective D-2-like agonists such as quinelorane, quinpirole, and 7-OH-DPAT. Instead, D-2-like agonists induced a significant decrease in wakefulness and increases in both slow-wave sleep and PS. The effects of DA were mimicked, however, by application of clonidine, a selective alpha(2) adrenoceptor agonist, and blocked by co-application of RX821002, a selective antagonist Of alpha(2) adrenoceptors.Conclusions: Our results indicate that DA inhibits PS in the peri-locus coeruleus alpha via excitation Of alpha(2) adrenoceptors, but application of D-2-like agonists to the same region markedly decreases wakefulness and increases both slow-wave sleep and PS. This effect may be responsible for the excessive daytime sleepiness and sleep attacks induced by antiparkinsonian dopaminergic agents.