Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; Penn State Addiction Center for Translation, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Brain Res Bull. 2022 Oct 15;189:163-173. doi: 10.1016/j.brainresbull.2022.08.022. Epub 2022 Aug 28.
Opioid use disorder (OUD), like other substance use disorders (SUDs), is widely understood to be a disorder of persistent relapse. Despite the use of three FDA-approved medications for OUD, typically in conjunction with behavioral treatments, relapse rates remain unacceptably high. Whereas medication assisted therapy (MAT) reduces the risk of opioid overdose mortality, the benefits of MAT are negated when people discontinue the medications. Currently approved medications present barriers to efficient use, including daily visits to a treatment center or work restrictions. With spiking increases in opioid relapse and death, it is imperative to identify new treatments that can reduce the risk of relapse. Recent evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs), currently FDA-approved to treat obesity and type two diabetes, may be promising candidates to reduce relapse. GLP-1RAs have been shown to reduce relapse in rats, whether elicited by cues, drug, and/or stress. However, GLP-1RAs also can cause gastrointestinal malaise, and therefore, in humans, the medication typically is titrated up to full dose when initiating treatment. Here, we used a rodent model to test whether cue- and drug-induced heroin seeking can be reduced by the GLP-1RA, liraglutide, when the dose is titrated across the abstinence period and prior to test. The results show this titration regimen is effective in reducing both cue-induced heroin seeking and drug-induced reinstatement of heroin seeking, particularly in rats with a history of high drug-taking. Importantly, this treatment regimen had no effect on either circulating glucose or insulin. GLP-1RAs, then, appear strong candidates for the non-opioid prevention of relapse to opioids.
阿片类使用障碍（OUD），与其他物质使用障碍（SUD）一样，被广泛认为是一种持续复发的疾病。尽管使用了三种获得 FDA 批准的 OUD 药物，通常与行为治疗一起使用，但复发率仍然高得令人无法接受。尽管药物辅助治疗（MAT）降低了阿片类药物过量死亡的风险，但当人们停止使用药物时，MAT 的益处就会被抵消。目前批准的药物在使用上存在障碍，包括每天去治疗中心或工作限制。由于阿片类药物复发和死亡的风险不断增加，因此必须确定新的治疗方法来降低复发风险。最近的证据表明，胰高血糖素样肽-1 受体激动剂（GLP-1RAs），目前被 FDA 批准用于治疗肥胖症和 2 型糖尿病，可能是降低复发风险的有前途的候选药物。GLP-1RAs 已被证明可减少大鼠的复发，无论是由线索、药物和/或压力引起的。然而，GLP-1RAs 也会引起胃肠道不适，因此，在人类中，在开始治疗时，药物通常会逐渐增加到全剂量。在这里，我们使用一种啮齿动物模型来测试 GLP-1RA 利拉鲁肽是否可以在戒断期间和测试前调整剂量来减少线索和药物引起的海洛因寻求。结果表明，这种滴定方案可有效减少线索诱导的海洛因寻求和药物诱导的海洛因寻求的恢复，特别是在有高药物使用史的大鼠中。重要的是，这种治疗方案对循环葡萄糖或胰岛素没有影响。因此，GLP-1RAs 似乎是预防阿片类药物复发的非阿片类药物的有力候选药物。
