The food intake-suppressive effects of glucagon-like peptide-1 receptor signaling in the ventral tegmental area are mediated by AMPA/kainate receptors
The food intake-suppressive effects of glucagon-like peptide-1 receptor signaling in the ventral tegmental area are mediated by AMPA/kainate receptors
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DOI：
10.1152/ajpendo.00413.2013
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发表时间：
2013-12-01
影响因子：
5.1
通讯作者：
Hayes, Matthew R.
中科院分区：
文献类型：
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作者：
Mietlicki-Baase, Elizabeth G.;Ortinski, Pavel I.;Hayes, Matthew R.
腹侧被盖区 (VTA) 的胰高血糖素样肽 1 受体 (GLP-1R) 激活在生理上与控制可口食物摄入有关。在这里，我们测试了 VTA GLP-1R 激活的食物摄入抑制作用是否是由 VTA 内的谷氨酸信号介导的。 VTA 内注射 GLP-1R 激动剂 exendin-4 (Ex-4) 主要通过减少膳食量来减少大鼠可口的高脂肪食物摄入量；这些作用部分是通过谷氨酸 AMPA/红藻氨酸而不是 NMDA 受体信号传导介导的。其他行为数据表明，VTA 内特异性表达的 GLP-1R 可以部分介导全身施用 Ex-4 的摄入和体重抑制作用，这提供了一种有趣的可能性，即该受体群可能与食物摄入控制具有临床相关性。 VTA 内 Ex-4 迅速增加 VTA 内酪氨酸羟化酶水平，表明 GLP-1R 激活调节 VTA 多巴胺能信号传导。电生理学数据为这一假设提供了进一步的证据，显示 Ex-4 增加了 AMPA 介导的电流频率并降低了 VTA 多巴胺神经元中的配对/脉冲比。总之，这些数据提供了 GLP-1R 激动剂在中脑边缘奖赏系统中控制可口食物摄入的新机制。
Glucagon-like peptide-1 receptor (GLP-1R) activation in the ventral tegmental area (VTA) is physiologically relevant for the control of palatable food intake. Here, we tested whether the food intake-suppressive effects of VTA GLP-1R activation are mediated by glutamatergic signaling within the VTA. Intra-VTA injections of the GLP-1R agonist exendin-4 (Ex-4) reduced palatable high-fat food intake in rats primarily by reducing meal size; these effects were mediated in part via glutamatergic AMPA/kainate but not NMDA receptor signaling. Additional behavioral data indicated that GLP-1R expressed specifically within the VTA can partially mediate the intake- and body weight-suppressive effects of systemically administered Ex-4, offering the intriguing possibility that this receptor population may be clinically relevant for food intake control. Intra-VTA Ex-4 rapidly increased tyrosine hydroxylase levels within the VTA, suggesting that GLP-1R activation modulates VTA dopaminergic signaling. Further evidence for this hypothesis was provided by electrophysiological data showing that Ex-4 increased the frequency of AMPA-mediated currents and reduced the paired/pulse ratio in VTA dopamine neurons. Together, these data provide novel mechanisms by which GLP-1R agonists in the mesolimbic reward system control for palatable food intake.