Salsolinol modulation of dopamine neurons.

Salsolinol modulation of dopamine neurons.
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DOI:
10.3389/fnbeh.2013.00052
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发表时间:
2013
影响因子:
3
通讯作者:
Ye JH
Ye JH
中科院分区:
医学3区
文献类型:
--
作者:
Xie G;Krnjević K;Ye JH

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猪毛菜醇是一种存在于人类和大鼠大脑中的四氢异喹啉,是多巴胺和乙醛的缩合产物,乙醛是乙醇的第一代谢产物。先前在体内获得的证据链接salsolinol与中脑边缘多巴胺(DA)系统:salsolinol是自我管理到后方的腹侧被盖区(pVTA)的大鼠;内VTA管理salsolinol诱导一个强大的条件性位置偏好,并增加多巴胺释放在丘脑核(NAc)。然而,潜在的神经机制尚不清楚。在这里,我们提出了一个概述的一些最近的研究就这一主题。电生理研究表明,在pVTA的DA神经元是猪毛菜醇的目标。在大鼠的急性脑切片中,猪毛菜醇增加了兴奋性,并加速了pVTA中多巴胺神经元的持续放电。有趣的是,猪毛菜醇的这种作用涉及多种突触前和突触后机制,包括:(1)使多巴胺神经元去极化;(2)通过激活对多巴胺神经元的GABA能输入上的μ阿片受体-这降低了GABA能活性-多巴胺神经元被解除抑制;和(3)通过多巴胺1型受体的激活增强突触前多巴胺能传递到多巴胺神经元,很可能位于神经元末梢这些新的机制可能有助于在体内观察到的salsolinol的奖励/增强性能。
Salsolinol, a tetrahydroisoquinoline present in the human and rat brains, is the condensation product of dopamine and acetaldehyde, the first metabolite of ethanol. Previous evidence obtained in vivo links salsolinol with the mesolimbic dopaminergic (DA) system: salsolinol is self-administered into the posterior of the ventral tegmental area (pVTA) of rats; intra-VTA administration of salsolinol induces a strong conditional place preference and increases dopamine release in the nucleus accumbens (NAc). However, the underlying neuronal mechanisms are unclear. Here we present an overview of some of the recent research on this topic. Electrophysiological studies reveal that DA neurons in the pVTA are a target of salsolinol. In acute brain slices from rats, salsolinol increases the excitability and accelerates the ongoing firing of dopamine neurons in the pVTA. Intriguingly, this action of salsolinol involves multiple pre- and post-synaptic mechanisms, including: (1) depolarizing dopamine neurons; (2) by activating μ opioid receptors on the GABAergic inputs to dopamine neurons – which decreases GABAergic activity – dopamine neurons are disinhibited; and (3) enhancing presynaptic glutamatergic transmission onto dopamine neurons via activation of dopamine type 1 receptors, probably situated on the glutamatergic terminals. These novel mechanisms may contribute to the rewarding/reinforcing properties of salsolinol observed in vivo.
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