Ethanol dually modulates GABAergic synaptic transmission onto dopaminergic neurons in ventral tegmental area:: Role of μ-opioid receptors
Ethanol dually modulates GABAergic synaptic transmission onto dopaminergic neurons in ventral tegmental area:: Role of μ-opioid receptors
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DOI：
10.1016/j.neuroscience.2008.01.040
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发表时间：
2008-04-22
期刊：
影响因子：
3.3
通讯作者：
Ye, J. -H.
中科院分区：
文献类型：
--
作者：
Xiao, C.;Ye, J. -H.
起源于腹侧被盖区（VTA）的中边缘多巴胺能系统与乙醇的奖励特性有关。VTA多巴胺能神经元受gaba能神经支配。gaba能剂的应用改变了乙醇的消耗量。然而，目前尚不清楚急性乙醇如何调节gaba能输入到VTA中的多巴胺能神经元。本报告描述了临床相关浓度（10-40 mM）的乙醇对抑制性突触后电流（IPSCs）的双重调节。诱导多能干细胞由GABA(A)受体介导，并在大鼠急性中脑切片VTA多巴胺能神经元上记录。急性应用乙醇可降低诱导多能干细胞的振幅，增加诱导多能干细胞的成对脉冲比。乙醇降低了诱导多能干细胞的频率，但没有降低诱导多能干细胞的幅度。然而，乙醇对存在河豚毒素的微型多能干细胞没有影响。这些数据表明，乙醇通过突触前机制抑制gaba能突触向多巴胺能神经元的传递，并且乙醇的抑制作用依赖于gaba能神经元的放电。GABA(B)受体拮抗剂CGP 52432的应用没有改变乙醇对IPSCs的抑制作用。相反，一种多阿片受体激动剂tyr - d - ala - gly - n - me - ph - gly -ol脑啡肽（DAMGO）可以沉默VTA GAIBAergic神经元并抑制IPSCs。值得注意的是，在饱和浓度的DAMGO （3 μ M）存在下，乙醇增强了剩余的IPSCs。因此，乙醇可以双重调节向VTA多巴胺能神经元的GAIBAergic传递。乙醇调节依赖于VTA GAIBAergic神经元的活性，该神经元被mu-阿片受体的激活所抑制。乙醇对gaba能传递的双重调节可能是酒精成瘾的重要机制。(c) 2008 ibro。Elsevier Ltd.出版。版权所有。
The mesolimbic dopaminergic system, originating from the ventral tegmental area (VTA) is implicated in the rewarding properties of ethanol. VTA dopaminergic neurons are under the tonic control of GABAergic innervations. Application of GABAergic agents changes ethanol consumption. However, it is unclear how acute ethanol modulates GABAergic inputs to dopaminergic neurons in the VTA. This report describes ethanol at clinically relevant concentrations (10-40 mM) dually modulates inhibitory postsynaptic currents (IPSCs). IPSCs were mediated by GABA(A) receptors and were recorded from VTA dopaminergic neurons in acute midbrain slices of rats. Acute application of ethanol reduced the amplitude and increased the paired pulse ratio of evoked IPSCs. Ethanol lowered the frequency but not the amplitude of spontaneous IPSCs. Nevertheless, ethanol had no effect on miniature IPSCs recorded in the presence of tetrodotoxin. These data indicate that ethanol inhibits GABAergic synaptic transmission to dopaminergic neurons by presynaptic mechanisms, and that ethanol inhibition depends on the firing of GABAergic neurons. Application of CGP 52432, a GABA(B) receptor antagonist, did not change ethanol inhibition of IPSCs. Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol enkephalin (DAMGO), a mu-opioid receptor agonist, conversely, silenced VTA GAIBAergic neurons and inhibited IPSCs. Of note, in the presence of a saturating concentration of DAMGO (3 mu M), ethanol potentiated the remaining IPSCs. Thus, ethanol dually modulates GAIBAergic transmission to dopaminergic neurons in the VTA. Ethanol modulation depends on the activity of VTA GAIBAergic neurons, which were inhibited by the activation of mu-opioid receptors. This dual modulation of GABAergic transmission by ethanol may be an important mechanism underlying alcohol addiction. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.