Ethanol Intake and Hypothalamic CRH Receptor Type 2

描述（由申请人提供）：拟议研究的目的是研究下丘脑腹内侧（VMH）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耗，导致酒精摄入量增加。中央给药CRH受体激动剂，如促肾上腺皮质激素释放激素和尿皮质素，可减少食物、水和乙醇的摄入。研究表明，电刺激或注射CRH后，下丘脑下丘脑的食物摄入量会减少，这与食欲和食物摄入的调节有关。第一个目的中包含的研究检查了在小鼠的有限通道程序中，向VMH注射CRH-R2激动剂和拮抗剂对酒精消耗的影响。这些研究的结果将确定VMH中CRH-R2的活性是否在调节酒精自我给药中发挥作用。第二个目的是通过使用几种不同的酒精偏好小鼠和非偏好小鼠，将酒精摄入量和偏好与VMH中CRH-R2和尿皮质素III（一种内源性CRH-R2激动剂）的基础水平联系起来。

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.