Binge-eating effects on hindbrain mu-opioid activity.

暴饮暴食是大多数饮食失调的显著特征。卡路里限制的历史和对美味食物的过度消费是参与依赖国家的暴饮暴食行为的两个主要变量。本项目的目的是研究反复限制卡路里和获取美味食物的雌性大鼠在阿片类药物控制尾部脑干功能方面发生的变化。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类药物机制来调节的。这一假说将通过mU-阿片受体mRNA的原位杂交标记、早期即时基因c-Fos蛋白产物的免疫组织化学染色和神经电生理技术来验证。这些方法将使我们能够确定暴饮暴食是如何改变尾部脑干类阿片受体的(特定目标1)。此外，我们将确定中枢阿片活动如何改变孤束核中胃肠道反应神经元对胃负荷的摄食、神经元激活(特定目标2)和单位活动(特定目标3)。这一系列研究的长期目标是了解卡路里限制和美味食物的重复循环如何导致参与食物摄取的动态平衡过程的神经机制的变化。这个项目的独特之处在于，它将评估尾部脑干感觉对维持暴饮暴食的适应。因此，这个项目的发现对于确定暴饮暴食相关饮食障碍、神经性暴食症(BN)和暴饮暴食障碍(Bed)的持续因素和潜在治疗方法将特别相关。

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).