The hypothalamic neuropeptide melanin-concentrating hormone acts in the nucleus Accumbens to modulate feeding Behavior and forced-swim performance
The hypothalamic neuropeptide melanin-concentrating hormone acts in the nucleus Accumbens to modulate feeding Behavior and forced-swim performance
复制标题
DOI：
10.1523/jneurosci.1714-04.2005
复制
发表时间：
2005-03-16
影响因子：
5.3
通讯作者：
DiLeone, RJ
中科院分区：
文献类型：
--
作者：
Georgescu, D;Sears, RM;DiLeone, RJ
黑色素浓集激素（MCH）是一种下丘脑神经肽，在摄食和能量平衡中具有重要作用。啮齿类动物MCH受体（MCH 1 R）高度表达于核壳（AcSh），这是一个在调节食欲行为中非常重要的区域。在这里，我们建立了MCH和MCH 1 R在调解下丘脑边缘电路，调节进食和相关行为的作用。在强迫游泳试验中，将MCH 1 R受体拮抗剂直接递送到AcSh阻断进食并产生抗抑郁样作用，而AcSh内注射MCH具有相反的作用。表达研究表明，MCH 1 R存在于脑啡肽和强啡肽阳性的AcSh中型棘神经元。AcSh外植体的生化分析表明，MCH信号阻断多巴胺诱导的AMPA谷氨酸受体亚基GluR 1在Ser（845）的磷酸化。最后，食物剥夺，而不是其他的压力，刺激cAMP反应元件结合蛋白依赖的途径选择性地在MCH神经元的下丘脑，这表明这些神经元是响应一组特定的生理相关条件。这项工作确定了一种新的下丘脑-乙酰胆碱回路，影响食欲行为和介导的抗抑郁活性的MCH 1 R拮抗剂。
Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a prominent role in feeding and energy homeostasis. The rodent MCH receptor (MCH1R) is highly expressed in the nucleus accumbens shell (AcSh), a region that is important in the regulation of appetitive behavior. Here we establish a role for MCH and MCH1R in mediating a hypothalamic-limbic circuit that regulates feeding and related behaviors. Direct delivery of an MCH1R receptor antagonist to the AcSh blocked feeding and produced an antidepressant-like effect in the forced swim test, whereas intra-AcSh injection of MCH had the opposite effect. Expression studies demonstrated that MCH1R is present in both the enkephalin- and dynorphin-positive medium spiny neurons of the AcSh. Biochemical analysis in AcSh explants showed that MCH signaling blocks dopamine-induced phosphorylation of the AMPA glutamate receptor subunit GluR1 at Ser(845). Finally, food deprivation, but not other stressors, stimulated cAMP response element-binding protein-dependent pathways selectively in MCH neurons of the hypothalamus, suggesting that these neurons are responsive to a specific set of physiologically relevant conditions. This work identifies a novel hypothalamic-AcSh circuit that influences appetitive behavior and mediates the antidepressant activity of MCH1R antagonists.