Glucagon-like peptide-1 receptor agonist, exendin-4, reduces reinstatement of heroin-seeking behavior in rats.
Glucagon-like peptide-1 receptor agonist, exendin-4, reduces reinstatement of heroin-seeking behavior in rats.
复制标题
胰高血糖素样肽-1受体激动剂exendin-4减少大鼠海洛因寻求行为的复发。
DOI：
10.1097/fbp.0000000000000609
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发表时间：
2021-06-01
影响因子：
1.6
通讯作者：
Grigson PS
中科院分区：
文献类型：
--
作者：
Douton JE;Augusto C;Stoltzfus B;Carkaci-Salli N;Vrana KE;Grigson PS
阿片类药物使用障碍（OUD）每天导致近130名美国人死亡。因此，显然需要新的治疗途径。为此，研究报告了“饱腹感”剂，如胰高血糖素样肽-1受体（GLP-1 R）激动剂、毒蜥外泌肽-4（Ex-4），降低对成瘾药物如可卡因、尼古丁、酒精和羟考酮的反应，但没有对海洛因进行研究。在本研究中，我们使用奖励贬值模型，其中大鼠避免摄入预测药物可用性的糖精溶液，以测试2.4 μg/kg Ex-4对响应自然奖励线索（即，糖精）和对线索和药物诱导的海洛因寻求。结果表明，在16天的戒断期和测试日用Ex-4处理减少了线索诱导的海洛因寻求。药物诱导的海洛因寻求的恢复也减少了Ex-4，但只有当使用1小时，而不是6小时，预处理时间。用Ex-4治疗并没有改变糖精提示的摄入量，当药物在船上时，但用Ex-4治疗的历史确实增加了在后来的消退试验中对糖精提示的接受度。最后，用Ex-4处理不改变体重，但与在核壳中食欲素1受体（OX 1）mRNA表达的增加相关。总之，这些结果首次表明GLP-1 R激动剂治疗可减少线索诱导的海洛因寻求和药物诱导的海洛因寻求复发。因此，GLP-1 R激动剂可作为人类OUD的有效治疗。
Opioid use disorder (OUD) causes the death of nearly 130 Americans daily. It is evident then that new avenues for treatment are needed. To this end, studies have reported that ‘satiety’ agents such as the glucagon-like peptide-1 receptor (GLP-1R) agonist, exendin-4 (Ex-4), decreases responding for addictive drugs such as cocaine, nicotine, alcohol, and oxycodone, but no work has been done with heroin. In this study, we used a reward devaluation model in which rats avoid ingesting a saccharin solution that predicts drug availability to test the effects of 2.4 μg/kg Ex-4 on responding for a natural reward cue (i.e., saccharin) and on cue- and drug-induced heroin seeking. The results showed that treatment with Ex-4 during the 16-day abstinence period and on the test day decreased cue-induced heroin seeking. Drug-induced reinstatement of heroin seeking also was reduced by Ex-4, but only when using a 1h, but not a 6h, pretreatment time. Treatment with Ex-4 did not alter intake of the saccharin cue when the drug was on board, but a history of treatment with Ex-4 did increase acceptance of the saccharin cue in later extinction trials. Finally, treatment with Ex-4 did not alter body weight, but was associated with an increase in Orexin 1 receptor (OX1) mRNA expression in the nucleus accumbens shell. Taken together, these findings are the first to show that treatment with a GLP-1R agonist can reduce both cue-induced heroin seeking and drug-induced reinstatement of heroin seeking. As such, a GLP-1R agonist may serve as an effective treatment for OUD in humans.