THE MESOLIMBIC DOPAMINE-ACTIVATING PROPERTIES OF ETHANOL ARE ANTAGONIZED BY MECAMYLAMINE
THE MESOLIMBIC DOPAMINE-ACTIVATING PROPERTIES OF ETHANOL ARE ANTAGONIZED BY MECAMYLAMINE
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DOI：
10.1016/0014-2999(93)90434-j
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发表时间：
1993-11-09
影响因子：
5
通讯作者：
SODERPALM, B
中科院分区：
文献类型：
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作者：
BLOMQVIST, O;ENGEL, JA;SODERPALM, B
有人提出，乙醇可能与中枢烟碱型乙酰胆碱受体相互作用，从而为经常观察到的乙醇和尼古丁的高消耗提供了基础。在目前的体内微透析研究中，乙醇(2.5g/kg)适度增加了大鼠伏隔核中多巴胺的溢出。中枢烟碱型乙酰胆碱受体拮抗剂甲乙胺在剂量(1.0 mg/kg)中完全抵消了这种效应，但本身并不改变多巴胺的溢出。乙醇还可增加二羟基苯乙酸和高香草酸的外溢，但甲氨基甲胺(1.0 mg/kg)不能改变这一作用。此外，L芳香族氨基酸脱羧酶抑制剂NSD1015对乙醇引起的中脑边缘多巴胺终末区3，4-二羟基苯丙氨酸蓄积的促进作用，可被甲氨基甲胺(3.0和6.0 mg/kg)完全拮抗，而甲氨基甲胺本身无此作用。乙醇和甲乙胺都不会改变纹状体或大脑皮层中儿茶酚胺的合成率。这些结果进一步证明，乙醇诱导的中脑边缘多巴胺系统的激活(增加多巴胺的合成和释放)可能是通过刺激中枢烟碱型乙酰胆碱受体介导的。提示中枢烟碱型乙酰胆碱受体拮抗剂可用于酒精中毒的治疗。
It has been suggested that ethanol may interact with the central nicotinic acetylcholine receptor, thus providing a basis for the often observed high consumption of both ethanol and nicotine. In the present in vivo microdialysis study, ethanol (2.5 g/kg) moderately increased dopamine overflow in the rat nucleus accumbens. The central nicotinic acetylcholine receptor antagonist mecamylamine totally counteracted this effect in a dose (1.0 mg/kg) that did not alter dopamine overflow per se. Ethanol also increased the overflow of dihydroxyphenylacetic acid and homovanillic acid, but this effect was not altered by mecamylamine (1.0 mg/kg). Furthermore, the ethanol-induced enhancement of 3,4-dihydroxyphenylalanine accumulation in the mesolimbic dopamine terminal area after NSD 1015 (an inhibitor of l-aromatic amino acid decarboxylase) was completely antagonized by mecamylamine in doses (3.0 and 6.0 mg/kg) that exerted no effects per se. Neither ethanol nor mecamylamine changed the catecholamine synthesis rate in the striatum or the cerebral cortex. These results provide further evidence that ethanol-induced activation of the mesolimbic dopamine system (increased dopamine synthesis and release) may be mediated via stimulation of central nicotinic acetylcholine receptors. It is suggested that antagonists of central nicotinic acetylcholine receptors may be useful in the treatment of alcoholism.