Acute glucagon-like peptide-1 receptor agonist liraglutide prevents cue-, stress-, and drug-induced heroin-seeking in rats.
Acute glucagon-like peptide-1 receptor agonist liraglutide prevents cue-, stress-, and drug-induced heroin-seeking in rats.
复制标题
DOI：
10.1097/fbp.0000000000000685
复制
发表时间：
2022-08-01
影响因子：
1.6
通讯作者：
Nyland, Jennifer E.
中科院分区：
文献类型：
--
作者：
Douton, Joaquin E.;Acharya, Nikhil K.;Stoltzfus, Brooke;Sun, Dongxiao;Grigson, Patricia S.;Nyland, Jennifer E.
物质使用障碍是具有挑战性的治疗，由于其复发的性质。在过去的十年中，阿片类药物使用障碍一直是对公共卫生的威胁，被疾病控制和预防中心宣布为流行病。这是一个悲惨的情况，考虑到目前只有三种有效但不理想的治疗方法可以防止阿片类药物复发。最近的研究表明，调节饥饿和饱腹感的激素也可以调节滥用药物的动机行为。例如，胰高血糖素样肽-1（GLP-1）的短效类似物（一种调节稳态摄食的肠促胰岛素激素）已被证明在几天或几周内给药时会减少对奖励刺激（如食物、可卡因、海洛因和尼古丁）的反应。这可能在治疗期间作为一种有效的辅助剂;然而，当急性使用时，它是否有效，以在停止使用和开始治疗阿片类药物成瘾的药物之间架起患者的桥梁，目前尚不清楚。在这里，我们测试了长效GLP-1类似物利拉鲁肽对海洛因寻求的急性影响。在有海洛因自我给药经验的大鼠中，我们发现皮下给予0.3 mg/kg利拉鲁肽急性剂量可有效预防暴露于三种主要促发因素后的药物寻求：药物相关线索、应激（育亨宾诱导）和药物本身。最后，我们证实了药物寻求的减少不是由于运动障碍，因为利拉鲁肽在转棒测试中没有显著改变表现。因此，急性使用GLP-1类似物可作为一种新的有效的非阿片类药物治疗桥梁。
Substance use disorder is challenging to treat due to its relapsing nature. In the last decade, opioid use disorder has been a threat to public health, being declared an epidemic by the Centers for Disease Control and Prevention. This is a tragic situation, considering there currently are only three effective, yet not ideal, treatments to prevent relapse to opioids. Recent research has shown that hormones that modulate hunger and satiety also can modulate motivated behavior for drugs of abuse. For example, the short-acting analog of glucagon-like peptide-1 (GLP-1), an incretin hormone that regulates homeostatic feeding, has been shown to reduce responding for rewarding stimuli such as food, cocaine, heroin, and nicotine when administered over several days or weeks. This may serve as an effective adjuvant during treatment; however, whether it would be effective when used acutely to bridge a patient between cessation of use and onset of medication for the treatment of an opioid addiction is unknown. Here, we tested the acute effects of the longer-acting GLP-1 analog, liraglutide, on heroin seeking. In rats with heroin self-administration experience, we found that subcutaneous administration of an acute dose of 0.3 mg/kg liraglutide was effective in preventing drug seeking after exposure to three major precipitators: drug-associated cues, stress (yohimbine-induced), and the drug itself. Finally, we confirmed that the reduction in drug seeking is not due to a locomotor impairment, as liraglutide did not significantly alter performance in a rotarod test. As such, acute use of GLP-1 analogs may serve as a new and effective non-opioid bridge to treatment.