Role of ghrelin in drug abuse and reward-relevant behaviors: a burgeoning field and gaps in the literature.

A R Revitsky, L C Klein
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引用次数: 13

Abstract

Ghrelin is a gut-brain hormone that regulates energy balance through food consumption. While ghrelin is well known for its role in hypothalamic activation and homeostatic feeding, more recent evidence suggests that ghrelin also is involved in hedonic feeding through the dopaminergic reward pathway. This paper investigated how ghrelin administration (intraperitoneal, intracerebroventricular, or directly into dopaminergic reward-relevant brain regions) activates the dopaminergic reward pathway and associated reward-relevant behavioral responses in rodents. A total of 19 empirical publications that examined one or more of these variables were included in this review. Overall, ghrelin administration increases dopamine levels in the nucleus accumbens, as well as reward-relevant behaviors such as food (both standard chow and palatable foods) and alcohol consumption. Ghrelin administration also increases operant responding for sucrose, and conditioned place preference. Following a review of the small body of literature examining the effects of ghrelin administration on the dopamine reward pathway, we present a model of the relationship between ghrelin and dopaminergic reward activation. Specifically, ghrelin acts on ghrelin receptors (GHS-R1A) in the ventral tegmental area (VTA) and lateral dorsal tegmental nucleus (LDTg) to stimulate the mesolimbic dopamine reward pathway, which results in increased rewarding behaviors in rodents. Results from this review suggest that selective antagonism of the ghrelin system may serve as potential treatment for addictive drug use. This review highlights gaps in the literature, including a lack of examination of sex- or age-related differences in the effects of ghrelin on dopamine reward processes. In light of vulnerability to drug abuse among female and adolescent populations, future studies should target these individual difference factors.

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胃饥饿素在药物滥用和奖励相关行为中的作用:一个新兴领域和文献空白。
胃饥饿素是一种肠-脑激素,通过食物消耗调节能量平衡。虽然胃饥饿素因其在下丘脑激活和稳态进食中的作用而闻名,但最近的证据表明,胃饥饿素也通过多巴胺能奖励途径参与享乐性进食。本文研究了ghrelin(腹腔、脑室或直接进入多巴胺能奖励相关脑区)如何激活啮齿动物的多巴胺能奖励通路和相关的奖励相关行为反应。本综述共收录了19篇检验了其中一个或多个变量的实证出版物。总的来说,胃饥饿素增加了伏隔核中的多巴胺水平,以及与奖励相关的行为,如食物(标准食物和美味食物)和饮酒。胃促生长素的施用也增加了对蔗糖的操作性反应和条件性位置偏好。在回顾了一小部分研究胃饥饿素对多巴胺奖励通路影响的文献后,我们提出了胃饥饿素和多巴胺能奖励激活之间关系的模型。具体来说,胃饥饿素作用于胃饥饿素受体(GHS-R1A)腹侧被盖区(VTA)和外侧背被盖核(LDTg),刺激中边缘多巴胺奖励通路,导致啮齿动物奖励行为增加。这篇综述的结果表明,胃饥饿素系统的选择性拮抗可能是成瘾药物使用的潜在治疗方法。这篇综述强调了文献中的空白,包括缺乏对胃饥饿素对多巴胺奖励过程影响的性别或年龄相关差异的研究。鉴于女性和青少年群体对药物滥用的脆弱性,未来的研究应针对这些个体差异因素。
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