Effects of glucagon-like peptide 1 analogs on alcohol intake in alcohol-preferring vervet monkeys.
Effects of glucagon-like peptide 1 analogs on alcohol intake in alcohol-preferring vervet monkeys.
复制标题
胰高血糖素样肽 1 类似物对嗜酒长尾猴酒精摄入量的影响。
DOI：
10.1007/s00213-018-5089-z
复制
发表时间：
2019
影响因子：
3.4
通讯作者：
Fink-Jensen,Anders
中科院分区：
文献类型：
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作者：
Thomsen,Morgane;Holst,JensJuul;Molander,Anna;Linnet,Kristian;Ptito,Maurice;Fink-Jensen,Anders
背景啮齿类动物的临床前研究表明，胰高血糖素样肽-1 (GLP-1) 受体刺激对饮酒具有抑制作用。尚未研究 GLP-1 受体刺激对灵长类动物酒精摄入量的影响。方法我们对 GLP-1 受体激动剂艾塞那肽和利拉鲁肽对嗜酒的雄性非洲黑长尾猴的饮酒量进行了安慰剂对照研究。对被选择自愿饮酒的猴子进行至少 10 天的基线饮酒观察，并根据酒精摄入量分配到药物或媒介物（每组 n = 11-12）。猴子每天 4 小时可以接触酒精。在第一项研究中，猴子每周接受一次 0.04 mg/kg 艾塞那肽或载体治疗，持续 5 周，以获得稳态血浆水平。在第二项研究中，猴子每天接受利拉鲁肽（增加剂量，10 至 50 μg/kg/天）或媒介物治疗，持续两周。在这两项研究中，在药物滴定期间暂停饮酒。然后，再次每天 4 小时提供酒精，治疗持续 2 周，在此期间记录酒精摄入量。药物清除后继续观察酒精摄入量。结果与媒介物相比，利拉鲁肽和艾塞那肽在较小程度上显着减少了酒精摄入量，且没有引起任何呕吐迹象，并且对饮水量没有影响。结论本研究首次证明 GLP-1 受体激动剂可以减少非人类灵长类动物的自愿饮酒。这些数据证实了 GLP-1 受体激动剂在治疗酒精使用障碍中的潜在用途。
BackgroundPreclinical studies in rodents have demonstrated inhibitory effects of glucagon-like peptide-1 (GLP-1) receptor stimulation on alcohol consumption. The effects of GLP-1 receptor stimulation on alcohol intake in primates have not been investigated.MethodsWe performed placebo-controlled studies on the effects of the GLP-1 receptor agonists exenatide and liraglutide on alcohol consumption in alcohol-preferring male African vervet monkeys. Monkeys selected for voluntary alcohol drinking were observed for at least 10 days of baseline drinking and allocated to drug or vehicle (n= 11–12 per group) balanced with respect to alcohol intake. Monkeys had access to alcohol 4 h/day. In a first study, monkeys were treated with exenatide 0.04 mg/kg or vehicle once weekly for 5 weeks to obtain steady-state plasma levels. In a second study, monkeys were treated daily with liraglutide (increasing dosing, 10 to 50 μg/kg/day) or vehicle over 2 weeks. In both studies, access to alcohol was suspended during drug up-titration. Then, alcohol was again made available 4 h/day and treatment was continued for 2 weeks, during which alcohol intake was recorded. Observation of alcohol intake was continued for a week of drug washout.ResultsLiraglutide and to a lesser extent exenatide significantly reduced alcohol consumption without causing any signs of emesis and with no effect on water intake as compared to vehicle.ConclusionsThe present study demonstrates for the first time that GLP-1 receptor agonists can reduce voluntary alcohol drinking in non-human primates. The data substantiate the potential usefulness of GLP-1 receptor agonists in the treatment of alcohol use disorder.