Glucagon-like peptide-1 receptor agonist, liraglutide, reduces heroin self-administration and drug-induced reinstatement of heroin-seeking behaviour in rats
Glucagon-like peptide-1 receptor agonist, liraglutide, reduces heroin self-administration and drug-induced reinstatement of heroin-seeking behaviour in rats
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DOI：
10.1111/adb.13117
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发表时间：
2021-11-21
影响因子：
3.4
通讯作者：
Grigson, Patricia S.
中科院分区：
文献类型：
--
作者：
Douton, Joaquin E.;Horvath, Nelli;Grigson, Patricia S.
药物成瘾是一种慢性脑部疾病，其特征是无节制地使用某种物质。由于其复发的性质，成瘾很难治疗，因为个人即使在长期戒酒后也可能复发，而且正是在这段时间里，他们最容易受到过量服药的影响。在美国，阿片类药物过量几十年来一直在增加，这使得寻找新的治疗方法来帮助患者保持戒酒和防止过量死亡势在必行。最近，高血糖素样多肽-1(GLP-1)受体激动剂在减少药物滥用的动机行为方面显示出了希望。在这项研究中，我们测试了GLP-1类似物利拉鲁肽(LIR)在减少海洛因成瘾样行为方面的有效性，以及与治疗相关的潜在副作用。结果表明，每天皮下注射LIR(0.1 mg/kg sc)可延长大鼠服用海洛因的潜伏期，减少海洛因自我给药，防止海洛因自我给药的升级，并减少药物诱导的大鼠海洛因寻找行为的恢复。然而，在我们的研究中，1小时的预处理时间太短，不能减少线索诱导的寻求。此外，我们发现，虽然LIR(0.1、0.3、0.6和1.0 mg/kg sc)支持对LIR糖精线索的条件性味觉回避，但它不会诱导海洛因幼稚或海洛因经验的大鼠摄入止吐高岭土。此外，0.1毫克/公斤的LIR不会对食物摄入量或体重造成很大的干扰。总体而言，数据显示，LIR在减少海洛因摄入和寻求海洛因方面是有效的，剂量不会导致不适，对食物摄入量和体重增加的影响不大。
Drug addiction is a chronic brain disease characterized by the uncontrolled use of a substance. Due to its relapsing nature, addiction is difficult to treat, as individuals can relapse following even long periods of abstinence and, it is during this time, that they are most vulnerable to overdose. In America, opioid overdose has been increasing for decades, making finding new treatments to help patients remain abstinent and prevent overdose deaths imperative. Recently, glucagon-like peptide-1 (GLP-1) receptor agonists have shown promise in reducing motivated behaviours for drugs of abuse. In this study, we test the effectiveness of the GLP-1 analogue, liraglutide (LIR), in reducing heroin addiction-like behaviour, and the potential side effects associated with the treatment. We show that daily treatment with LIR (0.1 mg/kg sc) increases the latency to take heroin, reduces heroin self-administration, prevents escalation of heroin self-administration and reduces drug-induced reinstatement of heroin-seeking behaviour in rats. A 1-h pretreatment time, however, was too short to reduce cue-induced seeking in our study. Moreover, we showed that, while LIR (0.1, 0.3, 0.6 and 1.0 mg/kg sc) supported conditioned taste avoidance of a LIR-paired saccharin cue, it did not elicit intake of the antiemetic kaolin in heroin-naive or heroin-experienced rats. Further, 0.1 mg/kg LIR did not produce great disruptions in food intake or body weight. Overall, the data show that LIR is effective in reducing heroin taking and heroin seeking at doses that do not cause malaise and have a modest effect on food intake and body weight gain.