右美托咪定通过激活海马α_(2)肾上腺素能受体改善大鼠酒精戒断症状

Dexmedetomidine improves alcohol withdrawal symptom via activatingα_(2)adrenergic receptor in rat hippocampus

本文旨在研究α_(2)肾上腺素能受体激动剂右美托咪定对酒精依赖大鼠戒断症状的影响及作用机制,以期为酒精戒断综合征(alcohol withdrawal syndrome,AWS)的治疗提供科学依据。成年Sprague-Dawley(SD)雄性大鼠连续28 d饮用6%酒精水溶液建立饮酒模型,然后停止饮酒以诱导AWS。用酶联免疫吸附法测定大鼠脑组织蓝斑核及海马去甲肾上腺素的含量。在大鼠AWS显著时分别腹腔注射5、10、20μg/kg右美托咪定,并记录戒断症状变化,部分大鼠预先在海马注射α_(2)肾上腺素能受体拮抗剂育亨宾。结果显示,与对照组相比,酒精戒断6 h组大鼠AWS评分和再次饮酒量显著提高,末次饮酒组和戒断6 h组海马及蓝斑核去甲肾上腺素含量显著升高。右美托咪定干预后,戒断6 h组AWS评分及海马去甲肾上腺素含量均显著降低,而育亨宾可以逆转右美托咪定的上述作用。以上结果提示,右美托咪定可能通过激活海马α_2肾上腺素能受体改善酒精依赖大鼠戒断症状。

The purpose of this study was to investigate the effects ofα_(2) adrenergic receptor agonist dexmedetomidine on withdrawal symptoms in alcohol-dependent rats and the underlying mechanism,so as to provide a scientific basis for the treatment of alcohol withdrawal syndrome(AWS).Adult Sprague-Dawley(SD)male rats were orally administered with 6%aqueous alcohol continuously for 28 d to establish alcohol drinking model,and then stopped drinking to induce AWS.Enzyme-linked immunosorbent assay(ELISA)was used to determine the content of norepinephrine(NE)in the locus coeruleus and hippocampus of rats.Dexmedetomidine(5,10,and 20μg/kg)was intraperitoneally injected respectively when the rats showed significant AWS.In some rats,α_(2) adrenergic receptor antagonist yohimbine was injected into hippocampus in advance.The results showed that,compared with the control group,the 6 h withdrawal group exhibited significantly increased AWS score and amount of repeat drinking.The NE contents in hippocampus and locus coeruleus of the last drinking and the 6 h withdrawal groups were significantly increased compared with those of the control group.Dexmedetomidine intervention significantly decreased AWS score and hippocampus NE content in the 6 h withdrawal group,while yohimbine could reverse these effects of dexmedetomidine.These results suggest that dexmedetomidine might improve the withdrawal symptoms in alcohol-dependent rats via activatingα_(2) adrenergic receptor.