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Neuroendocrine Response to Exogenous Ghrelin Administration, Combined With Alcohol, in Heavy-Drinking Individuals: Findings From a Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study
International Journal of Neuropsychopharmacology ( IF 4.8 ) Pub Date : 2021-02-03 , DOI: 10.1093/ijnp/pyab004
Mehdi Farokhnia 1, 2, 3 , Kelly M Abshire 1 , Aaron Hammer 1 , Sara L Deschaine 1 , Anitha Saravanakumar 4 , Enoch Cobbina , Zhi-Bing You 5 , Carolina L Haass-Koffler 1, 6, 7 , Mary R Lee 1 , Fatemeh Akhlaghi 4 , Lorenzo Leggio 1, 2, 7, 8, 9
Affiliation  

Background 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. Methods 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. Results 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. Conclusion 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.

中文翻译:

重度饮酒者对外源性生长素释放肽给药与酒精的神经内分泌反应:随机、双盲、安慰剂对照人体实验室研究的结果

背景 越来越多的证据已经确定了促食欲激素ghrelin 在饮酒行为中的作用。因此,生长素释放肽系统可能代表酒精使用障碍的潜在药物治疗靶点。Ghrelin 调节几种神经内分泌途径,例如食欲、代谢和压力相关的激素,这在饮酒的情况下尤其相关。本研究的目的是全面评估酗酒者对外源性生长素释放肽给药和酒精的神经内分泌反应。方法 这是一项随机、交叉、双盲、安慰剂对照的人体实验室研究,其中包括 2 种实验性酒精给药范例:iv 酒精自我给药和 iv 酒精钳夹。每个范例包括 2 个平衡的 iv ghrelin 或安慰剂给药疗程。在每个疗程中重复采集血液样本,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。结果 尽管存在一些统计学差异,但在 2 种酒精给药模式中的发现是一致的:与安慰剂相比,静脉注射生长素释放肽在急性期和整个疗程期间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。在生长素释放肽与安慰剂的对比中,也发现了较低水平的瘦素和较高水平的醛固酮。结论 这些发现,
更新日期:2021-02-03
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