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: 7032229
• 负责人: Aaron G Roseberry
• 金额: $ 10.32万
• 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 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7032229
• 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）： 肥胖已迅速成为美国一个严重的健康问题，最近的报告估计，美国近一半的成年人口属于超重或肥胖**。虽然许多旨在了解能量稳态的遗传和分子调节的研究都集中在下丘脑的中心，但很明显其他大脑区域也参与了进食的调节。有证据表明，内源性奖励途径，包括中脑边缘多巴胺系统，在进食和体重的调节中发挥作用。然而，中脑边缘多巴胺系统和进食状态如何相互作用和相互调节尚不清楚。该提案中的实验将利用电生理学来检查腹侧被盖区（VTA）多巴胺神经元的活动如何通过进食和进食相关参数进行调节。 瘦素和胰岛素通过在下丘脑中的作用介导对能量稳态的一些影响，但瘦素和胰岛素也能够调节中脑边缘多巴胺系统中与进食相关的改变。然而，瘦素和胰岛素对进食行为涉及的奖赏系统影响的分子机制尚未确定。也有人提出，中脑边缘多巴胺系统可能与可口食物的摄入有关，例如高脂肪或高糖的食物。然而，奖励系统与美味食物摄入之间相互作用的机制尚未确定。因此，该特定目标的实验将利用电生理学来确定瘦素、胰岛素和美味食物的摄入对 VTA 多巴胺神经元活性的影响。这些研究将为进食状态与中脑边缘多巴胺系统活动之间的相互作用提供有价值的信息，并可能为肥胖的预防和治疗提供潜在的目标。