Binge-eating effects on hindbrain mu-opioid activity.

暴饮暴食是大多数饮食失调的突出特征。热量限制的历史和过度食用高可口的食物是参与暴食行为的状态依赖性持久化的两个主要变量。本项目的目的是研究暴露于重复循环的热量限制和获得可口的食物的雌性大鼠尾侧脑干功能的μ-阿片样物质控制中发生的变化。提出的假设是，暴食的历史导致胃肠道感觉反馈的改变，这部分是通过中枢阿片机制介导的。该假设将通过使用原位杂交标记的μ-阿片受体mRNA，免疫组织化学染色的蛋白产物的早期直接基因，c-Fos，和神经电生理技术进行测试。这些方法将使我们能够确定暴饮暴食如何改变尾脑干μ阿片受体（具体目标1）。此外，我们将确定中枢μ阿片活性如何改变进食，神经元激活（具体目标2），以及胃肠道反应神经元在孤束核胃负荷（具体目标3）的单一单位活动。这一系列研究的长期目标是了解热量限制和获得可口食物的重复循环如何导致参与食物摄入稳态过程的神经机制发生改变。这个项目是独一无二的，因为它将评估尾脑干感觉适应维持暴食。因此，该项目的研究结果将特别有助于确定与暴食相关的饮食失调，神经性贪食症（BN）和暴食症（BED）的持续因素和潜在治疗方法。

Binge eating is a prominent characteristic of most eating disorders. A history of caloric restriction and the over-consumption of highly palatable foods are two main variables that participate in the state-dependent perpetuation of bingeing behavior. The objective of the current project is to investigate alterations that occur in the mu-opioid control of the caudal brainstem function in female rats exposed to a repeated cycle of calorie restriction and access to palatable foods. The proposed hypothesis is that a history of binge-like eating results in alterations in gastrointestinal sensory feedback, which are mediated, in part, through central opioid mechanisms. The hypothesis will be tested by using in situ hybridization labeling of the mu-opioid receptor mRNA, immunohistochemical staining of the protein product of the early immediate gene, c-Fos, and neuro-electrophysiological techniques. These approaches will allow us to determine how binge-like eating alters caudal brai nstem mu-opioid receptors (Specific Aim 1). In addition, we will determine how central mu-opioid activity alters feeding, neuronal activation (Specific Aim 2), and single unit activity of GI responsive neurons in the nucleus of the solitary tract to gastric loads (Specific Aim 3). The long-term objective of this line of research is to understand how repeated cycles of calorie restriction and access to palatable foods leads to alterations in the neural mechanisms involved in the homeostatic processes of food intake. This project is unique in that it will assess the caudal brainstem sensory adaptations to the maintenance of binge-like eating. The findings from this project, therefore, will be especially relevant for the identification of sustaining factors and potential treatments for binge-related eating disorders, bulimia nervosa (BN) and binge eating disorder (BED).