Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, Maryland, USA.
Center on Compulsive Behaviors, National Institutes of Health, Bethesda, Maryland, USA.
Int J Neuropsychopharmacol. 2021 Jul 14;24(6):464-476. doi: 10.1093/ijnp/pyab004.
Accumulating evidence has established a role for the orexigenic hormone ghrelin in alcohol-seeking behaviors. Accordingly, the ghrelin system may represent a potential pharmacotherapeutic target for alcohol use disorder. Ghrelin modulates several neuroendocrine pathways, such as appetitive, metabolic, and stress-related hormones, which are particularly relevant in the context of alcohol use. The goal of the present study was to provide a comprehensive assessment of neuroendocrine response to exogenous ghrelin administration, combined with alcohol, in heavy-drinking individuals.
This was a randomized, crossover, double-blind, placebo-controlled human laboratory study, which included 2 experimental alcohol administration paradigms: i.v. alcohol self-administration and i.v. alcohol clamp. Each paradigm consisted of 2 counterbalanced sessions of i.v. ghrelin or placebo administration. Repeated blood samples were collected during each session, and peripheral concentrations of the following hormones were measured: leptin, glucagon-like peptide-1, pancreatic polypeptide, gastric inhibitory peptide, insulin, insulin-like growth factor-1, cortisol, prolactin, and aldosterone.
Despite some statistical differences, findings were consistent across the 2 alcohol administration paradigms: i.v. ghrelin, compared to placebo, increased blood concentrations of glucagon-like peptide-1, pancreatic polypeptide, cortisol, and prolactin, both acutely and during the whole session. Lower levels of leptin and higher levels of aldosterone were also found during the ghrelin vs placebo session.
These findings, gathered from a clinically relevant sample of heavy-drinking individuals with alcohol use disorder, provide a deeper insight into the complex interplay between ghrelin and appetitive, metabolic, and stress-related neuroendocrine pathways in the context of alcohol use.
越来越多的证据表明，食欲激素 ghrelin 在觅酒行为中起作用。因此，ghrelin 系统可能代表了治疗酒精使用障碍的潜在药物靶点。ghrelin 调节几种神经内分泌途径，如食欲、代谢和应激相关激素，这些途径在酒精使用的背景下尤其相关。本研究的目的是综合评估外源性 ghrelin 给药与酒精联合对重度饮酒者的神经内分泌反应。
这是一项随机、交叉、双盲、安慰剂对照的人体实验室研究，包括 2 种实验性酒精给药方案：静脉内酒精自我给药和静脉内酒精钳夹。每个方案包括 2 次静脉内 ghrelin 或安慰剂给药的平衡对照。在每个疗程中反复采集血液样本，并测量以下激素的外周浓度：瘦素、胰高血糖素样肽-1、胰多肽、胃抑制肽、胰岛素、胰岛素样生长因子-1、皮质醇、催乳素和醛固酮。
尽管存在一些统计学差异，但这些发现在 2 种酒精给药方案中是一致的：与安慰剂相比，静脉内 ghrelin 给药既在急性时相，也在整个疗程中，增加了胰高血糖素样肽-1、胰多肽、皮质醇和催乳素的血液浓度。在 ghrelin 与安慰剂的疗程中，还发现瘦素水平较低，醛固酮水平较高。
这些发现来自于一组有酒精使用障碍的重度饮酒者的临床相关样本，深入了解了 ghrelin 与食欲、代谢和应激相关神经内分泌途径在酒精使用背景下的复杂相互作用。
