Hindbrain nucleus tractus solitarius glucagon-like peptide-1 receptor signaling reduces appetitive and motivational aspects of feeding
Hindbrain nucleus tractus solitarius glucagon-like peptide-1 receptor signaling reduces appetitive and motivational aspects of feeding
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DOI：
10.1152/ajpregu.00179.2014
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发表时间：
2014-08-15
影响因子：
2.8
通讯作者：
Grill, Harvey J.
中科院分区：
文献类型：
--
作者：
Alhadeff, Amber L.;Grill, Harvey J.
中枢胰高血糖素样肽-1受体（GLP-1R）信号通过影响多种神经过程，包括介导饱腹感、动机和奖励，减少食物摄入。虽然文献表明可分离的神经元和电路控制这些过程，但这一概念尚未得到充分的研究。GLP-1R信号在后脑内侧孤束核（mNTS）中的摄入抑制作用归因于与迷走神经传递的胃肠道饱食信号的相互作用，这些信号也由这些神经元处理。在这里，行为学和药理学技术被用来测试新的假设，即mNTS GLP-1R刺激后食物摄入量的减少也源于对食物动机性食欲行为的影响。结果表明，通过微量注射长效GLP-1R激动剂exendin-4激活mNTS GLP-1R，可以减少1)高脂饮食的摄入量，2)在渐进比例强化计划下对蔗糖的操作反应，以及3)对美味食物的条件位置偏好的表达。综上所述，这些数据表明，mNTS GLP-1R信号的摄入抑制作用不仅限于饱腹感，还包括通常归因于中脑和前脑神经元的对食物奖励和动机的影响。
Central glucagon-like peptide-1 receptor (GLP-1R) signaling reduces food intake by affecting a variety of neural processes, including those mediating satiation, motivation, and reward. While the literature suggests that separable neurons and circuits control these processes, this notion has not been adequately investigated. The intake inhibitory effects of GLP-1R signaling in the hindbrain medial nucleus tractus solitarius (mNTS) have been attributed to interactions with vagally transmitted gastrointestinal satiation signals that are also processed by these neurons. Here, behavioral and pharmacological techniques are used to test the novel hypothesis that the reduction of food intake following mNTS GLP-1R stimulation also results from effects on food-motivated appetitive behaviors. Results show that mNTS GLP-1R activation by microinjection of exendin-4, a long-acting GLP-1R agonist, reduced 1) intake of a palatable high-fat diet, 2) operant responding for sucrose under a progressive ratio schedule of reinforcement and 3) the expression of a conditioned place preference for a palatable food. Together, these data demonstrate that the intake inhibitory effects of mNTS GLP-1R signaling extend beyond satiation and include effects on food reward and motivation that are typically ascribed to midbrain and forebrain neurons.