Preclinical evidence suggests that ghrelin, a peptide synthesized by endocrine cells of the stomach and a key component of the gut-brain axis, is involved in alcohol seeking as it modulates both central reward and stress pathways. However, whether and how ghrelin administration may impact alcohol intake in humans is not clear. For, we believe, the first time, this was investigated in the present randomized, crossover, double-blind, placebo-controlled, human laboratory study. Participants were non-treatment-seeking alcohol-dependent heavy-drinking individuals. A 10-min loading dose of intravenous ghrelin/placebo (3 mcg kg^-1) followed by a continuous ghrelin/placebo infusion (16.9 ng/kg/min) was administered. During a progressive-ratio alcohol self-administration experiment, participants could press a button to receive intravenous alcohol using the Computerized Alcohol Infusion System. In another experiment, brain functional magnetic resonance imaging was conducted while participants performed a task to gain points for alcohol, food or no reward. Results showed that intravenous ghrelin, compared to placebo, significantly increased the number of alcohol infusions self-administered (percent change: 24.97±10.65, P=0.04, Cohen's d=0.74). Participants were also significantly faster to initiate alcohol self-administration when they received ghrelin, compared to placebo (P=0.03). The relationships between breath alcohol concentration and subjective effects of alcohol were also moderated by ghrelin administration. Neuroimaging data showed that ghrelin increased the alcohol-related signal in the amygdala (P=0.01) and modulated the food-related signal in the medial orbitofrontal cortex (P=0.01) and nucleus accumbens (P=0.08). These data indicate that ghrelin signaling affects alcohol seeking in humans and should be further investigated as a promising target for developing novel medications for alcohol use disorder.

中文翻译：

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外源性生长激素释放肽的给药会增加酒精的自我给药并调节重度饮酒的酒精依赖型个体的脑功能活动。

临床前证据表明，ghrelin是一种由胃内分泌细胞合成的肽，是肠脑轴的关键成分，与酒精搜寻有关，因为它可以调节中枢性奖励和应激途径。然而，生长素释放肽的施用是否以及如何影响人类的酒精摄入尚不清楚。我们相信，这是本研究首次在随机，交叉，双盲，安慰剂对照的人体实验室研究中进行了研究。参与者是不寻求治疗的依赖酒精的重度饮酒的人。静脉注射生长激素释放肽/安慰剂10分钟的剂量（3 mcg kg ^-1），然后连续进行生长素释放肽/安慰剂输注（16.9 ng / kg / min）。在逐步进行酒精自我管理实验期间，参与者可以使用计算机酒精输注系统按一个按钮以接收静脉内酒精。在另一个实验中，在参与者执行一项任务以获取酒精，食物或没有奖励的积分时，进行了大脑功能磁共振成像。结果显示，与安慰剂相比，静脉注射生长素释放肽显着增加了自行输注酒精的次数（百分比变化：24.97±10.65，P = 0.04，Cohen d = 0.74）。与安慰剂相比，参与者接受生长素释放肽释放激素后，他们开始酒精自我管理的速度也显着加快（P = 0.03）。ghrelin的给药也缓解了呼吸酒精浓度与酒精主观作用之间的关系。神经影像学数据显示，生长素释放肽增加杏仁核中与酒精有关的信号（P = 0.01）并调节眼眶额叶皮层（P = 0.01）和伏隔核中的食物相关信号（P = 0.08）。这些数据表明，ghrelin信号传导影响人类的饮酒，应进一步研究，将其作为开发针对酒精使用障碍的新型药物的有希望的靶标。