Ghrelin interacts with neuropeptide Y Y1 and opioid receptors to increase food reward.
Ghrelin interacts with neuropeptide Y Y1 and opioid receptors to increase food reward.
复制标题
DOI：
10.1210/en.2011-1606
复制
发表时间：
2012-03
期刊：
影响因子：
4.8
通讯作者：
K. Skibicka;Rozita H. Shirazi;C. Hansson;S. Dickson
中科院分区：
文献类型：
--
作者：
K. Skibicka;Rozita H. Shirazi;C. Hansson;S. Dickson
胃饥饿素是一种胃源性激素，是一种食欲肽，最近被证明可以有效地增加食物奖励行为。将ghrelin与中脑边缘系统和食物奖励行为联系起来的神经化学回路仍然不清楚。在这里，我们研究了神经肽Y（NPY）和阿片类药物对饥饿素对食物动机和摄入的影响。这两个系统都与中脑边缘腹侧被盖区（VTA）和奖励/动机控制有很好的联系。NPY通过激活NPY-Y1受体（NPY-Y1 R）介导ghrelin对食物摄入的影响;它们与动机行为的联系尚未探索。阿片类药物在饥饿素对食物导向行为的作用的任何方面都是未知的。大鼠进行训练，在一个渐进的比例蔗糖诱导的操作时间表来衡量食物奖励/动机行为。在操作性试验后立即测量食物摄入量。在单独的实验中，我们探讨了选择性NPY-Y1 R拮抗剂或阿片受体拮抗剂纳洛酮，脑室内或VTA内注射，对ghrelin诱导的食物奖励行为的抑制作用。心室ghrelin诱导的增加蔗糖动机的行为和食物摄入量完全阻断脑室内预处理与NPY-Y1 R拮抗剂或纳洛酮。VTA内Ghrelin诱导的蔗糖激发行为仅被VTA内纳洛酮阻断。相比之下，内VTA生长激素释放肽刺激的食物摄入量衰减，只有内VTA NPY-Y1封锁。最后，胃饥饿素输注与VTA μ-阿片受体表达升高相关。因此，我们确定中央神经肽Y和阿片类信号作为食物摄入和奖励效应的生长激素释放肽的必要介质和本地化这些相互作用的中脑边缘腹侧被盖区。
Ghrelin, a stomach-derived hormone, is an orexigenic peptide that was recently shown to potently increase food reward behavior. The neurochemical circuitry that links ghrelin to the mesolimbic system and food reward behavior remains unclear. Here we examined the contribution of neuropeptide Y (NPY) and opioids to ghrelin's effects on food motivation and intake. Both systems have well-established links to the mesolimbic ventral tegmental area (VTA) and reward/motivation control. NPY mediates the effect of ghrelin on food intake via activation of NPY-Y1 receptor (NPY-Y1R); their connection with respect to motivated behavior is unexplored. The role of opioids in any aspect of ghrelin's action on food-oriented behaviors is unknown. Rats were trained in a progressive ratio sucrose-induced operant schedule to measure food reward/motivation behavior. Chow intake was measured immediately after the operant test. In separate experiments, we explored the suppressive effects of a selective NPY-Y1R antagonist or opioid receptor antagonist naltrexone, injected either intracerebroventricularly or intra-VTA, on ghrelin-induced food reward behavior. The ventricular ghrelin-induced increase in sucrose-motivated behavior and chow intake were completely blocked by intracerebroventricular pretreatment with either an NPY-Y1R antagonist or naltrexone. The intra-VTA ghrelin-induced sucrose-motivated behavior was blocked only by intra-VTA naltrexone. In contrast, the intra-VTA ghrelin-stimulated chow intake was attenuated only by intra-VTA NPY-Y1 blockade. Finally, ghrelin infusion was associated with an elevated VTA μ-opioid receptor expression. Thus, we identify central NPY and opioid signaling as the necessary mediators of food intake and reward effects of ghrelin and localize these interactions to the mesolimbic VTA.