Xiao Cheng, Zhang Jingli, Krnjević Kresimir, Ye Jiang Hong
Department of Anesthesiology, New Jersey Medical School, Newark, NJ 07103-2714, USA.
Alcohol Clin Exp Res. 2007 Jul;31(7):1106-13. doi: 10.1111/j.1530-0277.2007.00405.x.
Although ethanol addiction is believed to be mediated by the mesolimbic dopamine system, originating from the ventral tegmental area (VTA), how acute ethanol increases the activity of VTA dopaminergic (DA) neurons remains unclear.
Patch-clamp recordings of spontaneous firings of DA and GABAergic neurons in the VTA in acute midbrain slices from rats.
Ethanol (20-80 mM) excites DA neurons, and more potently depresses firing of local GABAergic neurons. The ethanol-induced excitation of DA neurons is considerably attenuated by DAMGO (Tyr-d-Ala-Gly-N-Me-Phe-Gly-ol enkephalin), a mu-opioid agonist that suppresses firing of GABAergic neurons, or by naloxone, a general opioid antagonist. The ongoing opioid-induced facilitation of DA cell firing (revealed by naloxone) is enhanced by ethanol, probably by an increase in opioid release or action.
Ethanol excites VTA DA neurons at least partly by increasing ongoing opioid-mediated suppression of local GABAergic inhibition. This indirect mechanism may contribute significantly to the positively reinforcing properties of ethanol.
尽管人们认为乙醇成瘾是由中脑边缘多巴胺系统介导的，该系统起源于腹侧被盖区（VTA），但急性乙醇如何增加VTA多巴胺能（DA）神经元的活性仍不清楚。
对大鼠急性中脑切片中VTA的DA和GABA能神经元的自发放电进行膜片钳记录。
乙醇（20 - 80 mM）可兴奋DA神经元，且更有效地抑制局部GABA能神经元的放电。μ阿片受体激动剂DAMGO（酪氨酸 - d - 丙氨酸 - 甘氨酸 - N - 甲基 - 苯丙氨酸 - 甘氨酸脑啡肽）可抑制GABA能神经元的放电，阿片类拮抗剂纳洛酮均可使乙醇诱导的DA神经元兴奋作用明显减弱。乙醇可能通过增加阿片类物质的释放或作用，增强了阿片类物质对DA细胞放电的持续促进作用（由纳洛酮揭示）。
乙醇至少部分通过增加阿片类物质介导的对局部GABA能抑制的持续抑制来兴奋VTA的DA神经元。这种间接机制可能对乙醇的正性强化特性有显著贡献。
