The Role of NPY on the Alcohol Deprivation Effect

描述(申请人提供)：神经肽Y(NPY)和促肾上腺皮质激素释放因子(CRF)通过扩展的杏仁核内的变态反应对乙醇自我给药起相互调节作用。反复戒酒和复发可能会改变NPY和CRF之间的平衡，促进不受控制的乙醇摄入。酒精剥夺效应(ADE)是一种无节制饮酒的动物模型，其特征是在戒酒一段时间后，饮酒量显著增加。在这里，我们测试了一个假设，即低NPY信号和增加CRF信号，导致与ADE相关的不受控制的酒精饮酒。具体地说，我们将确定给予外源性NPY是否会防止获得和/或表达ADE(特异性目标1)，如果缺乏NPY的突变小鼠更容易受到ADE的影响(特异性目标2)，以及给予CRF拮抗剂是否可以防止获得和/或表达ADE(特异性目标3)。因此，本实验同时使用遗传学和药理学技术，以确定NPY和CRF信号系统在ADE引起的无控制乙醇自我给药中的作用。

DESCRIPTION (provided by applicant): It has been suggested that neuropeptide Y (NPY) and corticotropin releasing factor (CRF) exert a reciprocal regulation on ethanol self-administration via allostatic interactions within the extended amygdala. Repeated abstinence and relapse may alter the balance between NPY and CRF, promoting uncontrolled ethanol intake. The alcohol deprivation effect (ADE), characterized by robust increases of ethanol drinking following a period of ethanol abstinence, has been proposed to be an animal model of uncontrolled ethanol drinking. Here we test the hypothesis that low NPY signaling, and increased CRF signaling, contributes to the uncontrolled ethanol drinking associated with the ADE. Specifically, we will determine if administration of exogenous NPY will protect against the acquisition and/or expression of the ADE (Specific Aim 1), if mutant mice lacking NPY are more susceptible to the ADE (Specific Aim 2), and if administration of a CRF antagonist protects against the acquisition and/or expression of the ADE (Specific Aim 3). Thus, the proposed experiments employ both genetic and pharmacological techniques in order to determine the role of NPY and CRF signaling system on uncontrolled ethanol self-administration stemming from the ADE.