Yang X, Criswell H E, Breese G R
Department of Psychiatry and Anesthesiology, North Carolina Neurosciences Center, School of Medicine, University of North Carolina at Chapel Hill, 27599-7178, USA.
Alcohol Clin Exp Res. 1999 Jun;23(6):983-90.
A majority of alcoholics also smoke, suggesting that alcohol and nicotine share a common action on nicotinic cholinergic receptors.
Extracellular single-unit recording was used to investigate the effects of ethanol on responses to nicotine from rat cerebellar interneurons and medial septal neurons.
Nicotine produced inhibition from medial septal neurons, but increased neural activity of cerebellar interneurons. When ethanol was applied locally to cerebellar interneurons, the excitatory response to nicotine was enhanced in a dose-related manner. Nicotine-induced inhibition from medial septal neurons was reduced by ethanol from the majority of neurons, but a dose relationship for this inhibition by ethanol was not observed. Ethanol affected responses to nicotine from over 90% of all neurons investigated at these sites. Initially, it was established that the nicotinic antagonists, methyllycaconitine (MLA) and alpha-bungarotoxin, which affect a nicotinic cholinergic (nACh) receptor with an alpha7 subunit, had similar actions on responses to nicotine from individual medial septal cells and cerebellar interneurons. When MLA was tested against responses to nicotine from neurons in the two brain regions, MLA antagonized responses to nicotine from only 27% of the neurons rather than the 90% found for ethanol. This latter observation provided evidence that ethanol was affecting neurons with MLA-insensitive receptors. When the actions of ethanol on responses to nicotine were compared directly with the action of MLA on the same medial septal neurons, both ethanol and MLA caused a greater than 50% antagonism of the response to nicotine, indicative that nACh receptors with the alpha7 subunit were sensitive to ethanol.
Collectively, these data provide evidence that ethanol affects responses to nicotine not only from nACh receptors on medial septal cells and cerebellar interneurons containing an alpha7 subunit (i.e., MLA-sensitive receptors), but also from nACh receptor subtypes without this specific nACh receptor subunit (i.e., MLA-insensitive receptors).
大多数酗酒者也吸烟，这表明酒精和尼古丁对烟碱型胆碱能受体具有共同作用。
采用细胞外单单位记录法，研究乙醇对大鼠小脑中间神经元和内侧隔核神经元对尼古丁反应的影响。
尼古丁对内侧隔核神经元产生抑制作用，但增加了小脑中间神经元的神经活动。当将乙醇局部应用于小脑中间神经元时，对尼古丁的兴奋性反应以剂量相关的方式增强。大多数神经元的乙醇可降低尼古丁对内侧隔核神经元的抑制作用，但未观察到乙醇对该抑制作用的剂量关系。乙醇影响了这些部位超过90%的所有神经元对尼古丁的反应。最初，已确定影响含α7亚基的烟碱型胆碱能（nACh）受体的烟碱拮抗剂甲基lycaconitine（MLA）和α-银环蛇毒素，对单个内侧隔核细胞和小脑中间神经元对尼古丁的反应具有相似作用。当测试MLA对来自两个脑区神经元对尼古丁的反应时，MLA仅拮抗了27%的神经元对尼古丁的反应，而非乙醇作用的90%。后一观察结果提供了证据，表明乙醇正在影响具有MLA不敏感受体的神经元。当直接比较乙醇对尼古丁反应的作用与MLA对相同内侧隔核神经元的作用时，乙醇和MLA均导致对尼古丁反应的拮抗作用大于50%，表明含α7亚基的nACh受体对乙醇敏感。
总体而言，这些数据提供了证据，表明乙醇不仅影响内侧隔核细胞和含有α7亚基的小脑中间神经元（即MLA敏感受体）上的nACh受体对尼古丁的反应，还影响不含这种特定nACh受体亚基的nACh受体亚型（即MLA不敏感受体）对尼古丁的反应。
