Bhutada Pravinkumar Satyanarayan, Mundhada Yogita R, Bansod Kuldeep U, Umathe Sudhir N, Kahale Vivek P, Dixit Pankaj V, Mundhada Dharmendra R
Department of Pharmacology, Agnihotri College of Pharmacy, Pharmacology Division, Bapuji Wadi, Sindhi (Meghe), Wardha, India.
Behav Pharmacol. 2010 Mar;21(2):90-5. doi: 10.1097/FBP.0b013e328337be54.
Several reports show the involvement of neuronal nicotinic acetylcholine receptors (nAChRs) in the behavioral effects of ethanol, including ethanol drinking and relapse. Therefore, this study evaluated the effects of mecamylamine, a nAChR antagonist, on ethanol withdrawal signs. Ethanol dependence was induced in C57BL/6J mice by ethanol liquid diet administration. Animals were provided with nutritionally balanced control liquid diet (600 kcal/l) as their sole nutrient source on day 0; from days 1 to 4, 3% v/v of ethanol, followed by 6% v/v of ethanol (from days 5 to 7), and 10% v/v of ethanol (from days 8 to 10) were incorporated into the liquid diet. On day 11, ethanol liquid diet was replaced with nutritionally balanced control liquid diet, and ethanol withdrawal-induced physical signs were recorded. Results showed that acute administration of mecamylamine (1-4 mg/kg, intraperitoneally) dose-dependently attenuated ethanol withdrawal-induced signs, and these effects were comparable with those of diazepam (1-2 mg/kg, intraperitoneally). In addition, chronic administration of mecamylamine into ethanol diet-fed mice markedly attenuated the ethanol withdrawal sign scores, thus supporting the contention that nAChR is involved in ethanol dependence. In conclusion, our results suggest that mecamylamine exhibited inhibitory effects on ethanol withdrawal signs which could be mediated through nAChR.
多项报告显示，神经元烟碱型乙酰胆碱受体（nAChRs）参与了乙醇的行为效应，包括乙醇摄入和复吸。因此，本研究评估了nAChR拮抗剂美加明对乙醇戒断症状的影响。通过给予乙醇液体饲料诱导C57BL/6J小鼠产生乙醇依赖性。在第0天，给动物提供营养均衡的对照液体饲料（600千卡/升）作为其唯一的营养来源；从第1天到第4天，在液体饲料中加入3%（体积/体积）的乙醇，随后从第5天到第7天加入6%（体积/体积）的乙醇，从第8天到第10天加入10%（体积/体积）的乙醇。在第11天，将乙醇液体饲料替换为营养均衡的对照液体饲料，并记录乙醇戒断引起的身体症状。结果显示，急性给予美加明（1 - 4毫克/千克，腹腔注射）剂量依赖性地减轻了乙醇戒断引起的症状，且这些效应与地西泮（1 - 2毫克/千克，腹腔注射）相当。此外，对喂食乙醇饲料的小鼠长期给予美加明显著降低了乙醇戒断症状评分，从而支持了nAChR参与乙醇依赖的观点。总之，我们的结果表明，美加明对乙醇戒断症状具有抑制作用，这可能是通过nAChR介导的。
