Nicotinic receptor ligands reduce ethanol intake by high alcohol-drinking HAD-2 rats.
Nicotinic receptor ligands reduce ethanol intake by high alcohol-drinking HAD-2 rats.
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DOI：
10.1016/j.alcohol.2009.09.027
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发表时间：
2009-12
期刊：
影响因子：
--
通讯作者：
Rahman S
中科院分区：
文献类型：
--
作者：
Bell RL;Eiler BJ 2nd;Cook JB;Rahman S
神经元烟碱型乙酰胆碱受体(NAChRs)与包括乙醇在内的许多滥用药物的强化作用有关。本研究观察了nAChR部分激动剂胞苷和可能的nAChR拮抗剂洛贝林对HAD-2大鼠酒精饮酒的维持作用。成年雄性HAD-2大鼠从60日龄开始，每天22小时饮用乙醇(15%和30%，含水和食物)，连续12周，之后连续3天测试胞二磷胆碱(0.0，0.5和1.5 mg/kg)。给大鼠18d的洗脱期，然后给予洛贝林(0.0，1.0和5.0 mg/kg)，连续3d。分别于注射后1、4、22小时测量酒精摄入量。大鼠腹腔注射。就在熄灯前(1200小时)。试验第2天，与生理盐水相比，1.5 mg/kg剂量组小鼠酒精摄入量显著减少，0.5 mg/kg剂量组在4小时时间点显著减少。相反，洛贝林在每个测试日内的所有3个时间点都产生了显著的治疗主效应，与生理盐水相比，5.0 mg/kg剂量显著减少了每个测试日内每个时间点的乙醇摄入。这些发现提供了进一步的证据，表明nAChR的活动影响乙醇的摄入量，是治疗酒精依赖和复发的药物治疗开发的有前途的目标。
Neuronal nicotinic acetylcholine receptors (nAChRs) are implicated in the reinforcing effects of many drugs of abuse, including ethanol. The present study examined the efficacy of cytisine, a nAChR partial agonist, and lobeline, a putative nAChR antagonist, on the maintenance of ethanol drinking by HAD-2 rats. Adult male HAD-2 rats were given access to ethanol (15% and 30%, with ad lib water and food) 22 hr per day for 12 weeks, beginning at 60 days old, after which cytisine (0.0, 0.5 and 1.5 mg/kg) was tested for 3 consecutive days. The rats were given an 18 day wash-out period, and were then tested with lobeline (0.0, 1.0 and 5.0 mg/kg) for 3 consecutive days. Ethanol intake was measured at 1, 4 and 22 hours post-injection. Rats were injected i.p. just prior to lights out (1200 h). There was a significant main effect of cytisine treatment on the 2nd test day, with the 1.5 mg/kg dose significantly reducing ethanol intake at the 1 hr and 4 hr time-points, relative to saline, and the 0.5 mg/kg dose inducing a significant reduction at the 4 hr time-point. Conversely, lobeline treatment resulted in significant main effects of treatment for all 3 time points, within each test day, with the 5.0 mg/kg dose significantly reducing ethanol intake, relative to saline, at each time-point within each test day. These findings provide further evidence that activity at the nAChR influences ethanol intake and is a promising target for pharmacotherapy development for the treatment of alcohol dependence and relapse.
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2.3
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