The Role of Glutamate in the Control of Food Intake

肥胖是美国乃至整个西方社会发病率和死亡率的主要原因。 肥胖的发展往往与摄入过多的卡路里有关。显然，人们在家里吃饭 对各种刺激--生理、环境、情感和社会--的反应。然而，改善 我们对食物摄入量的神经控制的理解可能会提供具体的措施，通过这些措施肥胖可以 会被避开。终止进餐通常始于肠道感觉信号的传播。为 例如，对胃的机械刺激和对肠道的化学刺激都提供了 有助于终止食物摄取(饱腹感)的负面反馈。虽然迷走感觉神经元 已知将胃机械敏感信号和肠道化学敏感信号传递给大脑，很少是 已知神经递质和受体将这些信号从迷走神经传递到和 通过大脑。几年前，我们已经证明了N-甲基-D-天冬氨酸受体 (N-甲基-D-天冬氨酸受体)参与终止食物摄入。我们最近的研究结果表明，NMDA 受体通过改变胃运动活动来特异性地参与饱腹感。为了支持这一假设，我们 已经收集的证据表明，参与终止摄食的NMDA受体位于 背侧后脑，来自胃肠道的迷走神经运动纤维出现的地方。这些运动神经纤维作用于 通过M胆碱能受体调节胃排空率来控制食物摄入量。 此外，我们实验室的初步数据表明，P物质神经元和/或神经递质 受体可能是这种效应的重要神经底物。因此，我们的具体目标是 这次更新的应用概述如下：1)使用物理/化学消融来揭示中央和 全身性饮食增加的外周神经和神经化学底物 MK-801；2)利用行为和生理技术相结合的方法来确定 以及餐内胃运动功能改变与食物摄入量增加之间的定量关系 由MK-801唤起；以及，3)利用计算机辅助监测和分析膳食参数，在 联合急性和慢性给予NMDA受体拮抗剂，以确定其作用 NMDA受体控制自发进食量、24小时食物摄入量和体重。

Obesity accounts for significant morbidity and mortality in the USA, as well as Western societies in general. The development of obesity can often be linked to a consumption of excess calories. Clearly, people eat in response to a variety of stimuli--physiological, environmental, emotional and social. However, improving our understanding of the neural controls of food intake may provide concrete measures by which obesity can be avoided. Meal termination usually begins with the propagation of sensory signals from the gut. For example, both mechanical stimulation of the stomach, and chemical stimulation of the intestine provide negative feedback that contributes to termination of food intake (satiation). Although vagal sensory neurons are known to convey both gastric mechanosensitive and intestinal chemosensitive signals to the brain, little is known about the neurotransmitters and receptors that communicate these signals from the vagus, to and through the brain. Several years ago, we have demonstrated that ionotropic; N-methyl-D-aspartate receptors (NMDA receptors) participate in termination of food intake. Our more recent results indicate that NMDA receptors specifically participate in satiety by altering gastric motor activity. In support of this hypothesis, we have compiled evidence to suggest that NMDA receptors involved in termination of feeding are located in the dorsal hindbrain, where vagal motor fibers from the gastrointestinal tract arise. These motor fibers act to control food intake via muscarinic cholinergic receptors to modulate the rate of gastric emptying. Furthermore, preliminary data from our lab suggest that substance P neurons and/or neurotachyldnin receptors may be important neural substrates for this effect. Accordingly, the specific aims that we have outlined for this renewal application are: 1) to employ physical/chemical ablation to reveal the central and peripheral neural and neurochemical substrates that contribute to increases in meal size induced by systemic MK-801; 2) to utilize a combination of behavioral and physiological techniques to determine the qualitative and quantitative relationships between altered within-meal gastric motor functions and increased food intake evoked by MK-801; and, 3) to make use of computer-assisted monitoring and analysis of meal parameters, in combination with acute and chronic administration of NMDA receptor antagonists, to determine the role of NMDA receptors in control of spontaneous meal size, 24-hour food intake, and body weight.