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首页> 外文期刊>Addiction biology >Role of ghrelin in food reward: Impact of ghrelin on sucrose self-administration and mesolimbic dopamine and acetylcholine receptor gene expression
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Role of ghrelin in food reward: Impact of ghrelin on sucrose self-administration and mesolimbic dopamine and acetylcholine receptor gene expression

机译：ghrelin在食品奖励中的作用：ghrelin对蔗糖自我给药和中脑边缘多巴胺和乙酰胆碱受体基因表达的影响

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摘要

The decision to eat is strongly influenced by non-homeostatic factors such as food palatability. Indeed, the rewarding and motivational value of food can override homeostatic signals, leading to increased consumption and hence, obesity. Ghrelin, a gut-derived orexigenic hormone, has a prominent role in homeostatic feeding. Recently, however, it has emerged as a potent modulator of the mesolimbic dopaminergic reward pathway, suggesting a role for ghrelin in food reward. Here, we sought to determine whether ghrelin and its receptors are important for reinforcing motivation for natural sugar reward by examining the role of ghrelin receptor (GHS-R1A) stimulation and blockade for sucrose progressive ratio operant conditioning, a procedure used to measure motivational drive to obtain a reward. Peripherally and centrally administered ghrelin significantly increased operant responding and therefore, incentive motivation for sucrose. Utilizing the GHS-R1A antagonist JMV2959, we demonstrated that blockade of GHS-R1A signaling significantly decreased operant responding for sucrose. We further investigated ghrelin's effects on key mesolimbic reward nodes, the ventral tegmental area (VTA) and nucleus accumbens (NAcc), by evaluating the effects of chronic central ghrelin treatment on the expression of genes encoding major reward neurotransmitter receptors, namely dopamine and acetylcholine. Ghrelin treatment was associated with an increased dopamine receptor D5 and acetylcholine receptor nAChRβ2 gene expression in the VTA and decreased expression of D1, D3, D5 and nAChRα3 in the NAcc. Our data indicate that ghrelin plays an important role in motivation and reinforcement for sucrose and impacts on the expression of dopamine and acetylcholine encoding genes in the mesolimbic reward circuitry. These findings suggest that ghrelin antagonists have therapeutic potential for the treatment of obesity and to suppress the overconsumption of sweet food.
机译：饮食决定受非稳态因素（例如食物的适口性）的强烈影响。确实，食物的奖励和激励价值可以抵消体内平衡信号，从而导致食用量增加，从而导致肥胖。 Ghrelin是一种肠源性致食激素，在稳态喂养中具有重要作用。然而，最近，它已成为中脑边缘多巴胺能奖励途径的有效调节剂，表明生长素释放肽在食物奖励中的作用。在这里，我们试图通过检查ghrelin受体（GHS-R1A）刺激和蔗糖渐进比例操纵子调节的作用（该过程用于测量对人的动机驱动的过程）来确定ghrelin及其受体是否对增强天然糖分奖励的动机重要。获得奖励。外周和集中施用的生长素释放肽显着增加了手术反应，因此，激发了蔗糖的动机。利用GHS-R1A拮抗剂JMV2959，我们证明了GHS-R1A信号传导的阻断显着降低了操作员对蔗糖的反应。我们通过评估慢性中心ghrelin处理对编码主要奖励神经递质受体（即多巴胺和乙酰胆碱）的基因表达的影响，进一步研究了ghrelin对关键的中边缘边缘奖励结节，腹侧被盖区（VTA）和伏隔核（NAcc）的影响。 Ghrelin治疗与VTA中多巴胺受体D5和乙酰胆碱受体nAChRβ2基因表达增加以及NAcc中D1，D3，D5和nAChRα3表达减少有关。我们的数据表明，生长素释放肽在糖的动机和增强中起着重要作用，并影响中脑边缘奖励电路中多巴胺和乙酰胆碱编码基因的表达。这些发现表明，生长激素释放肽拮抗剂具有治疗肥胖症和抑制甜食过量消费的治疗潜力。

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