Feeding and the Regulation of Dopamine Neuronal Activity

进食和多巴胺神经元活动的调节

• 批准号: 6910469
• 负责人: Aaron G Roseberry
• 金额: $ 9.96万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6910469
• 关键词: appetite regulatory center; behavioral /social science research tag; brain electrical activity; dietary carbohydrates; dietary lipid; dopamine; eating; electrophysiology; genetically modified animals; hormone regulation /control mechanism; hypothalamus; insulin; laboratory mouse; leptin; limbic system; neuroregulation; nutrition related tag; reinforcer; tegmentum; voltage /patch clamp

DESCRIPTION (provided by applicant): Obesity has rapidly become a serious health problem in the United States, with recent reports estimating that nearly one half of the adult population in the US can be classified as overweight or obese**. While much of the research aimed at understanding the genetic and molecular regulation of energy homeostasis has focused on centers in the hypothalamus, it is clear that other brain regions are involved in the regulation of feeding. Evidence suggests that endogenous reward pathways, including the mesolimbic dopamine system play a role in the regulation of feeding and body weight. However, it is not clear how the mesolimbic dopamine system and feeding status interact with and regulate each other. The experiments in this proposal will utilize electrophysiology to examine how the activity of dopamine neurons in the ventral tegmental area (VTA) is modulated by feeding and feeding-related parameters. Leptin and insulin mediate some of their effects on energy homeostasis through their actions in the hypothalamus, but leptin and insulin are also able to modulate feeding related alterations in the mesolimbic dopamine system. However, the molecular mechanisms underlying the effects of leptin and insulin on the reward systems involved in feeding behavior have not been identified. It has also been suggested that the mesolimbic dopamine system may be involved in the intake of palatable foods such as those high in fat or sugar. However, the mechanisms underlying the interactions between reward systems and the intake of palatable foods have not been identified. Thus, the experiments in this specific aim will use electrophysiology to determine the effects of leptin, insulin, and the ingestion of palatable foods on the activity of VTA dopamine neurons. These studies will provide valuable information on the interactions between feeding state and the activity of the mesolimbic dopamine system, and may provide potential targets for the prevention and treatment of obesity.

描述（由申请人提供）： 在美国，肥胖症已迅速成为一个严重的健康问题，最近的报道估计，美国将近一半的成年人口可以归类为超重或肥胖**。尽管许多研究旨在了解能量体内稳态的遗传和分子调节的重点是下丘脑的中心，但很明显，其他大脑区域参与了喂养的调节。有证据表明，内源性奖励途径，包括中脱甲胺多巴胺系统在调节喂养和体重的调节中起作用。但是，尚不清楚中唇多巴胺系统和喂养状态如何相互作用并相互调节。该提案中的实验将利用电生理学来检查腹侧对接区域（VTA）中多巴胺神经元的活性如何通过喂养和喂养相关参数调节。 瘦素和胰岛素通过下丘脑的作用介导了它们对能量稳态的某些影响，但是瘦素和胰岛素也能够调节中左右多巴胺系统的相关变化。然而，尚未确定瘦素和胰岛素对喂养行为涉及的奖励系统作用的分子机制。还有人提出，中唇糖多巴胺系统可能参与摄入可口的食物，例如脂肪或糖高的食物。但是，尚未确定奖励系统与摄入可口食品之间相互作用的机制。因此，该特定目的的实验将使用电生理学来确定瘦素，胰岛素和可口食品对VTA多巴胺神经元活性的摄入。这些研究将提供有关饲养状态与中唇多巴胺系统活性之间相互作用的有价值的信息，并可能为预防和治疗肥胖提供潜在的目标。