Effects of Fentanyl-Adulterated Methamphetamine on Circulating Ghrelin in Rats

The appetite hormone ghrelin influences biological processes that are responsible for substance use disorder, which is related to alcohol and most abused drugs including cocaine, methamphetamine, nicotine, etc. In general, upregulation of the ghrelin system enhances drug cravings and substance use. Studies reported in the literature consistently demonstrated that the ghrelin system is associated with stimulants. However, research on opioids in combination with methamphetamine has not been reported. In this study, we examined the relationship of circulating ghrelin with the polydrug use of fentanyl and methamphetamine in male Sprague-Dawley rats, demonstrating for the first time that concurrent use of fentanyl and methamphetamine significantly increased plasma acyl-ghrelin (the active form of ghrelin) and total ghrelin concentrations. Additionally, the data also demonstrated for the first time that the use of fentanyl alone also significantly increased the plasma ghrelin concentrations. These findings imply that the ghrelin system could be a potential pharmacological target for the treatment of substance use disorders caused by polydrug use involving fentanyl and methamphetamine as well as the fentanyl use alone.饥饿激素（ghrelin）可调控与物质使用障碍相关的生物学过程，此类障碍与酒精及多数滥用药物（包括可卡因、甲基苯丙胺（methamphetamine）、尼古丁等）密切相关。一般而言，饥饿激素系统的上调会加剧药物渴求与物质使用行为。现有文献中的多项研究均一致表明，饥饿激素系统与中枢兴奋剂类药物存在关联。然而，目前尚无关于阿片类药物与甲基苯丙胺联合使用的相关研究报道。本研究以雄性斯普拉格-道利（Sprague-Dawley）大鼠为实验对象，探究了循环饥饿激素与芬太尼（fentanyl）联合甲基苯丙胺的多药滥用行为之间的关联。研究首次证实，芬太尼与甲基苯丙胺联合使用可显著提升血浆酰化饥饿激素（ghrelin的活性形式）及总饥饿激素的浓度。此外，本研究数据还首次发现，单独使用芬太尼也可显著升高血浆饥饿激素浓度。上述研究结果表明，饥饿激素系统有望成为治疗芬太尼联合甲基苯丙胺多药滥用及单纯芬太尼使用引发的物质使用障碍的潜在药理学靶点。