Quiroz Gabriel, Guerra-Díaz Nicolás, Iturriaga-Vásquez Patricio, Rivera-Meza Mario, Quintanilla María Elena, Sotomayor-Zárate Ramón
Programa de Doctorado en Farmacología, Universidad de Chile, Santiago, Chile.
Programa de Doctorado en Química, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
Behav Brain Res. 2018 Sep 3;349:169-176. doi: 10.1016/j.bbr.2018.04.038. Epub 2018 Apr 25.
Alcohol abuse is a worldwide health problem with high economic costs to health systems. Emerging evidence suggests that modulation of brain nicotinic acetylcholine receptors (nAChRs) may be a therapeutic target for alcohol dependence. In this work, we assess the effectiveness of four doses of erysodine (1.5, 2.0, 4.0 or 8.0 mg/kg/day, i.p.), a competitive antagonist of nAChRs, on voluntary ethanol consumption behavior in alcohol-preferring UChB rats, administered during three consecutive days. Results show that erysodine administration produces a dose-dependent reduction in ethanol consumption respect to saline injection (control group). The highest doses of erysodine (4 and 8 mg/kg) reduce (45 and 66%, respectively) the ethanol intake during treatment period and first day of post-treatment compared to control group. While, the lowest doses of erysodine (1.5 and 2 mg/kg) only reduce ethanol intake during one day of treatment period. These effective reductions in ethanol intake were 23 and 29% for 1.5 and 2 mg/kg erysodine, respectively. Locomotor activity induced by a high dose of erysodine (10 mg/kg) was similar to those observed with saline injection in control rats, showing that the reduction in ethanol intake was not produced by hypolocomotor effect induced by erysodine. This is the first report showing that erysodine reduces ethanol intake in UChB rats in a dose-dependent manner. Our results highlight the role of nAChRs in the reward effects of ethanol and its modulation as a potentially effective pharmacological alternative for alcohol dependence treatment.
酒精滥用是一个全球性的健康问题，给卫生系统带来了高昂的经济成本。新出现的证据表明，调节大脑烟碱型乙酰胆碱受体（nAChRs）可能是治疗酒精依赖的一个靶点。在这项研究中，我们评估了连续三天给予酒精偏好型UChB大鼠四种剂量的刺桐定碱（1.5、2.0、4.0或8.0mg/kg/天，腹腔注射）（一种nAChRs竞争性拮抗剂）对其自愿乙醇消费行为的有效性。结果表明，与注射生理盐水（对照组）相比，给予刺桐定碱可使乙醇消费量呈剂量依赖性减少。刺桐定碱的最高剂量（4和8mg/kg）与对照组相比，在治疗期和治疗后第一天分别减少了45%和66%的乙醇摄入量。而刺桐定碱的最低剂量（1.5和2mg/kg）仅在治疗期的一天内减少乙醇摄入量。对于1.5mg/kg和2mg/kg的刺桐定碱，乙醇摄入量的有效减少分别为23%和29%。高剂量刺桐定碱（10mg/kg）诱导的运动活性与对照组大鼠注射生理盐水时观察到的相似，表明乙醇摄入量的减少不是由刺桐定碱诱导的运动减少效应所致。这是首次报道刺桐定碱以剂量依赖性方式减少UChB大鼠的乙醇摄入量。我们的结果突出了nAChRs在乙醇奖赏效应中的作用及其调节作用，作为酒精依赖治疗的一种潜在有效药理学替代方法。
