Paradoxical modulation of short-term facilitation of dopamine release by dopamine autoreceptors
Paradoxical modulation of short-term facilitation of dopamine release by dopamine autoreceptors
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DOI：
10.1111/j.1471-4159.2007.04621.x
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发表时间：
2007-08-01
影响因子：
4.7
通讯作者：
Wightman, R. Mark
中科院分区：
文献类型：
--
作者：
Kita, Justin M.;Parker, Lauren E.;Wightman, R. Mark
电生理学研究表明，多巴胺能神经元在奖励相关行为的某些方面会爆发放电;然而，多巴胺释放和细胞放电之间的相关性尚不清楚。当采用模拟颅内自我刺激的复杂刺激模式时，多巴胺释放显示出易化和抑制成分（Montague et al. 2004）。了解这些多巴胺释放变化背后的生物学机制对于解开单位活动和神经递质释放之间的相关性是必要的。多巴胺自身受体对氯巴宁释放提供负反馈，在几秒的时间尺度上抑制释放。因此，我们研究了这种D-2受体，看看它是否是负责多巴胺释放的历史依赖性调制的生物学机制之一。在麻醉大鼠纹状体氯巴宁释放诱发与刺激列车，旨在促进多巴胺释放的变化。与公认的D-2介导的自身抑制一致，多巴胺释放的短期抑郁成分被D2拮抗剂raclopricle阻断，并被D-2受体激动剂quinpirole增强。令人惊讶的是，这些相同的药物对短期易化成分产生了类似的影响：雷氯必利减少，喹吡罗增加。这些数据表明，指挥控制施加多巴酚自身受体在短期神经适应多巴胺释放涉及抑制和矛盾，促进组件。
Electrophysiological studies have demonstrated that dopaminergic neurons burst fire during certain aspects of rewardrelated behavior; however, the correlation between dopamine release and cell firing is unclear. When complex stimulation patterns that mimic intracranial self -stimulation were employed, dopamine release was shown to exhibit facilitated as well as depressive components (Montague et al. 2004). Understanding the biological mechanisms underlying these variations in dopamine release is necessary to unravel the correlation between unit activity and neurotransmitter release. The dopamine autoreceptor provides negative feedback to cloparnine release, inhibiting release on the time scale of a few seconds. Therefore, we investigated this D-2 receptor to see whether it is one of the biological mechanisms responsible for the history-dependent modulation of dopamine release. Striatal cloparnine release in anesthetized rats was evoked with stimulus trains that were designed to promote the variability of dopamine release. Consistent with the well established D-2-mediated autoinhibition, the short-term depressive component of dopamine release was blocked by raclopricle, a D2 antagonist, and enhanced by quinpirole, a D-2-receptor agonist. Surprisingly, these same drugs exerted a similar effect on the short-term facilitated component: a decrease with raclopride and an increase with quinpirole. These data demonstrate that the commanding control exerted by doparnine autoreceptors over short-term neuroadaptation of dopamine release involves both inhibitory and paradoxically, facilitatory components.