Ethanol Intake and Hypothalamic CRH Receptor Type 2

描述(申请人提供)：本研究的目的是探讨下丘脑腹内侧区促肾上腺皮质激素释放激素2型受体(CRH-R2)与酒精摄入量的关系。酒精中毒被假设为无法调节酒精的食欲和消费，导致酒精摄入量增加。中枢应用促肾上腺皮质激素受体激动剂，如促肾上腺皮质激素释放激素和尿皮质激素，可以减少食物、水和乙醇的摄入量。有研究报告称，电刺激或向VMH注射CRH后，VMH的食物摄入量减少，这与VMH对食欲和食物消耗的调节有关。包含在第一个目的中的研究考察了将CRH-R2激动剂和拮抗剂注射到VMH对小鼠在有限进入过程中的酒精消耗的影响。这些研究的结果将确定VMH中CRH-R2的活性是否在酒精自我给药调节中发挥作用。第二个目的试图将酒精摄入和偏好与VMH中CRH-R2和内源性CRH-R2激动剂urocortin III的基础水平相关联，使用几种不同品系的酒精偏好和不偏好的小鼠。

DESCRIPTION (provided by applicant): The goal of the proposed studies is to investigate the relationship between corticotropin-releasing hormone type 2 receptors (CRH-R2) in the ventromedial hypothalamus (VMH) and ethanol intake. Alcoholism has been hypothesized as an inability to regulate appetite for and consumption of alcohol, resulting in increased intake of alcohol. Central administration of CRH receptor agonists, such as corticotropin-releasing hormone and urocortin, decreases intake of food, water and ethanol. The VMH is implicated in regulation of appetite and consumption of food by studies reporting a decrease in food intake following electrical stimulation or injection of CRH into the VMH. The studies contained in the first aim examine the effect of injection of CRH-R2 agonists and antagonists into the VMH on alcohol consumption in a limited access procedure in mice. Results from these studies will determine if activity at CRH-R2 in the VMH play a role in regulation of alcohol self-administration. The second aim attempts to correlate alcohol intake and preference with basal levels of CRH-R2 and urocortin III, an endogenous CRH-R2 agonist, in the VMH using several different strains of alcohol preferring versus non-preferring mice.