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首页> 外文期刊>Alcohol >Nicotinic receptor ligands reduce ethanol intake by high alcohol-drinking HAD-2 rats.
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Nicotinic receptor ligands reduce ethanol intake by high alcohol-drinking HAD-2 rats.

机译：烟碱受体配体可减少高酒精含量的HAD-2大鼠的乙醇摄入。

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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 libitum access to water and food) 22 h/day for 12 weeks, beginning at 60 days of age, 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 washout 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 h postinjection. Rats were injected intraperitoneally just before lights out (1200 h). There was a significant main effect of cytisine treatment on the second test day, with the 1.5 mg/kg dose significantly reducing ethanol intake at the 1- and 4-h time-points, relative to saline, and the 0.5 mg/kg dose inducing a significant reduction at the 4-h time-point. Conversely, lobeline treatment resulted in significant main effects of treatment for all three 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.
机译：神经元烟碱乙酰胆碱受体（nAChRs）与包括乙醇在内的许多滥用药物的增强作用有关。本研究检查了半胱氨酸（nAChR部分激动剂）和lobeline（假定的nAChR拮抗剂）对维持HAD-2大鼠饮酒的功效。从成年60天开始，成年雄性HAD-2大鼠每天22小时/天获得乙醇（15％和30％，自由饮水和食物），为期12周，之后再添加胱氨酸（0.0、0.5和1.5 mg / kg）连续3天进行测试。给大鼠提供18天的清除期，然后连续3天用卵磷脂（0.0、1.0和5.0 mg / kg）进行测试。在注射后1、4和22小时测量乙醇摄入量。在即将熄灭之前（1200小时）腹膜内注射大鼠。在第二个测试日，胱氨酸治疗具有显着的主要作用，相对于生理盐水，1.5 mg / kg剂量可在1和4 h时间点显着降低乙醇摄入量，而0.5 mg / kg剂量诱导在4小时的时间点显着减少。相反，在每天测试的三个时间点中，肝胆碱治疗均产生明显的主要治疗效果，相对于生理盐水而言，5.0 mg / kg的剂量在每个测试日中的每个时间点均显着降低了乙醇摄入量。这些发现提供了进一步的证据，表明nAChR的活性会影响乙醇的摄入，并且是用于治疗酒精依赖和复发的药物疗法的有希望的目标。

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