Ethanol Intake and Hypothalamic CRH Receptor Type 2

描述（由申请方提供）：拟定研究的目的是研究腹内侧下丘脑（VMH）中促肾上腺皮质激素释放激素2型受体（CRH-R2）与乙醇摄入量之间的关系。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。CRH受体激动剂如促肾上腺皮质激素释放激素和尿皮质素的中枢给药可减少食物、水和乙醇的摄入。VMH与食欲和食物消耗的调节有关，研究报告电刺激或将CRH注射到VMH后食物摄入减少。第一个目的中包含的研究检查了在小鼠中有限进入程序中将CRH-R2激动剂和拮抗剂注射到VMH中对酒精消耗的影响。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的调节中发挥作用。第二个目的是试图将酒精摄入量和偏好与VMH中CRH-R2和内源性CRH-R2激动剂urocortin III的基础水平相关联，使用几种不同的酒精偏好与非偏好小鼠品系。

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.