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首页> 外文期刊>Addiction biology >Ghrelin receptor (GHS-R1A) antagonism suppresses both operant alcohol self-administration and high alcohol consumption in rats
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Ghrelin receptor (GHS-R1A) antagonism suppresses both operant alcohol self-administration and high alcohol consumption in rats

机译：Ghrelin受体（GHS-R1A）拮抗作用可抑制大鼠自用酒精和高饮酒

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The mechanisms involved in alcohol use disorders are complex. It has been shown that ghrelin is an important signal for the control of body weight homeostasis, preferably by interacting with hypothalamic circuits, as well as for drug reward by activating the mesolimbic dopamine system. The ghrelin receptor (GHS-R1A) has been shown to be required for alcohol-induced reward. Additionally, ghrelin increases and GHR-R1A antagonists reduce moderate alcohol consumption in mice, and a single nucleotide polymorphism in the GHS-R1A gene has been associated with high alcohol consumption in humans. However, the role of central ghrelin signaling in high alcohol consumption is not known. Therefore, the role of GHS-R1A in operant self-administration of alcohol in rats as well as for high alcohol consumption in Long-Evans rats and in alcohol preferring [Alko alcohol (AA)] rats was studied here. In the present study, the GHS-R1A antagonist, JMV2959, was found to reduce the operant self-administration of alcohol in rats and to decrease high alcohol intake in Long-Evans rats as well as in AA rats. These results suggest that the ghrelin receptor signaling system, specifically GHS-R1A, is required for operant self-administration of alcohol and for high alcohol intake in rats. Therefore, the GHS-R1A may be a therapeutic target for treatment of addictive behaviors, such as alcohol dependence.
机译：饮酒障碍的机制很复杂。已经显示，生长素释放肽是控制体重稳态的重要信号，优选通过与下丘脑回路相互作用，以及通过激活中脑边缘多巴胺系统来获得药物奖励。 ghrelin受体（GHS-R1A）已被证明是酒精诱导的奖励所必需的。另外，生长素释放肽增加，GHR-R1A拮抗剂减少小鼠中的适度饮酒，并且GHS-R1A基因中的单核苷酸多态性与人类的高饮酒量有关。然而，中度生长激素释放肽信号传导在高饮酒中的作用尚不清楚。因此，本文研究了GHS-R1A在大鼠酒精有效自我管理中的作用，以及在Long-Evans大鼠和酒精偏爱[Alko alcohol（AA）]大鼠中高饮酒的作用。在本研究中，发现GHS-R1A拮抗剂JMV2959可减少大鼠的酒精操作性自我给药，并减少Long-Evans大鼠和AA大鼠的高酒精摄入量。这些结果表明生长素释放肽受体信号传导系统，特别是GHS-R1A，是酒精有效自我管理和大鼠高酒精摄入所必需的。因此，GHS-R1A可能是治疗成瘾行为（例如酒精依赖）的治疗靶标。

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