Voluntary ethanol intake in the rat: Effects of nicotinic acetylcholine receptor blockade or subchronic nicotine treatment
Voluntary ethanol intake in the rat: Effects of nicotinic acetylcholine receptor blockade or subchronic nicotine treatment
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DOI：
10.1016/s0014-2999(96)00583-3
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发表时间：
1996-10-31
影响因子：
5
通讯作者：
Soderpalm, B
中科院分区：
文献类型：
--
作者：
Blomqvist, O;Ericson, M;Soderpalm, B
已有研究表明，中脑边缘多巴胺的激活和乙醇的增强作用与中枢烟碱型乙酰胆碱受体的激活有关。为了验证这一假设，研究了两种尼古丁受体拮抗剂和亚慢性尼古丁治疗对低、中、高偏好酒精Wistar大鼠自愿饮酒(酒精6%v/v或水)的影响。在全身注射甲基戊胺(2 mg/kg)而不是六甲基铵(10 mg/kg)后，高偏好但不低偏好的大鼠减少了酒精摄入量，但不是酒精偏好。当亚慢性暴露于尼古丁(0.35 mg/kg，S.C.每天)中等偏爱的大鼠显著增加了它们的酒精摄入量和偏好。在中断尼古丁给药后，这种影响持续了一周以上。酒精摄入量与尼古丁攻击(0.35 mg/kg，S.C.)后的运动活动评分没有相关性。或者有探索性的运动活动。然而，在尼古丁(0.35 mg/kg，S.C.)后，探索性运动活动与运动活动分数都相关。乙醇(0.125 g/kg i.p.)挑战。急性尼古丁(0.35 mg/kg)刺激边缘前脑(包括伏隔核、嗅结节、杏仁核和隔核)的多巴胺释放增加，表现为单胺氧化酶抑制后3-甲氧基酪胺的积聚。或乙醇(2.5g/kg i.p.)在亚慢性暴露于尼古丁的动物中，与亚慢性车辆治疗的对照组相比。本研究结果进一步表明，中枢烟碱受体参与了介导乙醇增强特性的分子事件，并提示亚慢性尼古丁可增强中脑边缘多巴胺神经元对尼古丁和乙醇的反应性。对其临床意义进行了讨论。
It has been suggested that the mesolimbic dopamine activating and the reinforcing properties of ethanol involve activation of central nicotinic acetylcholine receptors. To test this hypothesis, the effects of two nicotinic receptor antagonists and of subchronic nicotine treatment on voluntary ethanol consumption (ethanol 6% v/v or water) were studied in ethanol low-, medium- or high-preferring Wistar rats. After systemic mecamylamine (2 mg/kg) but not hexamethonium (10 mg/kg) high- but not low-preferring rats decreased their ethanol intake but, however, not their ethanol preference. When subchronically exposed to nicotine (0.35 mg/kg, s.c. daily) medium-preferring rats markedly increased their ethanol intake and preference. This effect lasted for more than 1 week after interrupting nicotine administration. Ethanol intake levels did not correlate with locomotor activity scores after nicotine challenge (0.35 mg/kg, s.c.) or with exploratory locomotor activity. However, exploratory locomotor activity correlated with locomotor activity scores both after nicotine (0.35 mg/kg, s.c.) and ethanol (0.125 g/kg i.p.) challenge. Dopamine release, as indicated by accumulation of 3-methoxytyramine after monoamine oxidase inhibition, was increased in the limbic forebrain (including the nucleus accumbens, the olfactory tubercles, the amygdala and the septum) after acute nicotine (0.35 mg/kg s.c.) or ethanol (2.5 g/kg i.p.) in animals subchronically exposed to nicotine compared to subchronically vehicle-treated controls. The present results further implicate central nicotinic receptors in the molecular events mediating the reinforcing properties of ethanol, and suggest that subchronic nicotine enhances the responsiveness of mesolimbic dopamine neurons both to nicotine and to ethanol. Clinical implications are discussed.