Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite
Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite
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DOI：
10.1172/jci29867
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发表时间：
2006-12-01
影响因子：
15.9
通讯作者：
Horvath, Tamas L.
中科院分区：
文献类型：
--
作者：
Abizaid, Alfonso;Liu, Zhong-Wu;Horvath, Tamas L.
胃肠道激素ghrelin的目标是大脑，以促进食物摄入和肥胖。生长激素促分泌素1受体（GHSR）存在于控制能量代谢的下丘脑中心以及腹侧被盖区（VTA），这是一个对多种行为（包括进食）的动机方面很重要的区域。在这里，我们表明，在小鼠和大鼠中，生长激素释放肽绑定到腹侧被盖区的神经元，在那里它触发增加多巴胺神经元的活动，突触的形成，并在GHSR依赖的方式多巴胺在丘脑核营业额。直接腹侧被盖区给药的生长激素释放肽也引发喂养，而腹侧被盖区内递送的选择性GHSR拮抗剂阻断了循环生长激素释放肽的食欲促进作用，并减弱了禁食后的反弹喂养。此外，生长激素释放肽和GHSR缺陷小鼠表现出减弱的喂养反应，限制喂养时间表。两者合计，这些数据表明，中脑边缘的奖励电路的目标是由外周生长激素释放肽，以影响与进食相关的生理机制。
The gut hormone ghrelin targets the brain to promote food intake and adiposity. The ghrelin receptor growth hormone secretagogue 1 receptor (GHSR) is present in hypothalamic centers controlling energy metabolism as well as in the ventral tegmental area (VTA), a region important for motivational aspects of multiple behaviors, including feeding. Here we show that in mice and rats, ghrelin bound to neurons of the VTA, where it triggered increased dopamine neuronal activity, synapse formation, and dopamine turnover in the nucleus accumbens in a GHSR-dependent manner. Direct VTA administration of ghrelin also triggered feeding, while intra-VTA delivery of a selective GHSR antagonist blocked the orexigenic effect of circulating ghrelin and blunted rebound feeding following fasting. In addition, ghrelin- and GHSR-deficient mice showed attenuated feeding responses to restricted feeding schedules. Taken together, these data suggest that the mesolimbic reward circuitry is targeted by peripheral ghrelin to influence physiological mechanisms related to feeding.