Abstract
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.