Binge-eating effects on hindbrain mu-opioid activity.

暴饮暴食是大多数饮食失调的一个显著特征。热量限制的历史和过度食用美味的食物是两个主要的变量，参与状态依赖的暴饮暴食行为的延续。当前项目的目的是研究暴露于反复循环的卡路里限制和获得美味食物的雌性大鼠的尾侧脑干功能的mu-阿片控制发生的变化。提出的假设是，暴饮暴食的历史会导致胃肠道感觉反馈的改变，这在一定程度上是通过中枢阿片机制介导的。该假设将通过使用mu-阿片受体mRNA的原位杂交标记，早期直系基因c-Fos蛋白产物的免疫组织化学染色和神经电生理技术进行验证。这些方法将使我们能够确定暴饮暴食如何改变尾侧脑系统的mu-阿片受体（Specific Aim 1）。此外，我们将确定中枢mu-阿片活性如何改变进食、神经元激活（Specific Aim 2）和孤立束核GI反应神经元对胃负荷的单单位活性（Specific Aim 3）。这一研究的长期目标是了解热量限制和美味食物的反复循环如何导致参与食物摄入稳态过程的神经机制的改变。这个项目的独特之处在于，它将评估尾侧脑干对维持暴饮暴食的感觉适应。因此，该项目的研究结果对于确定暴饮暴食相关饮食失调、神经性贪食症（BN）和暴饮暴食症（BED）的维持因素和潜在治疗方法尤其重要。

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).