Rat Animal Models Core (RAMC)

描述(由申请人提供)：大鼠动物模型核心(RAMC)的长期目标是更好地了解过度饮酒(Etoh)发生和维持的分子神经生物学事件，以及这些神经生物学事件如何导致过度饮酒的长期后果。有待检验的总体假设是：(A)与过量饮酒有关的一些神经生物学事件发生在扩展杏仁核(E-AMYG)内；(B)在嗜酒、酗酒和酗酒的大鼠、HAD-1和HAD-2大鼠中，使用下文概述的过度饮酒程序能够检测到这些事件；(C)在E-AMYG内，特定部位损害结构[伏隔核壳(ACBsh)、中央杏仁核(Ce-AMYG)和终纹床核(BNST)]，改变过度饮酒的发展和/或维持；和(D)P和HAD大鼠在这些过度饮酒过程中的经历，导致与有效的酒精中毒动物模型标准相关的行为和/或生理变化(即，醉酒、耐受性和戒断症状的表现，以及酒精消耗量和/或酒精消费模式的变化)。过量饮酒被定义为在一段慢性时期内可重复和可持续的血液乙醇浓度(BECs)在100至150 mg%或更高的范围内。三种过度饮酒诱导方案将被用来反映(A)在黑暗周期[在黑暗中饮酒-多次程序访问(DIDMSA)]期间的暴饮式饮酒，大鼠在黑暗周期中接受三个相隔2小时的1小时访问周期；(B)通过延长重复酒精剥夺(PRAD)程序诱导依赖诱导过度饮酒，大鼠接受6周的初始乙醇访问，然后是2周的剥夺和2周的多次访问；和(C)酒精蒸气吸入戒断(过量)饮酒，采用3瓶选择测试程序(WID-3BC)，用于测量接触乙醇蒸气吸入和戒断乙醇蒸气吸入后的每个周期的摄入量。总体而言，该项目的成果将提供关于导致过度饮酒的发展和后果的复杂的分子神经生物学变化的宝贵信息，并有助于制定预防和/或治疗酗酒和酗酒的干预措施。

DESCRIPTION (provided by applicant): The long-range goals of the Rat Animal Models Core (RAMC) are to better understand the molecular neurobiological events underlying the development and maintenance of excessive ethanol (EtOH) drinking, and how these neurobiological events contribute to the long-range consequences of excessive EtOH drinking. The overall hypotheses to be tested are that (a) a number of neurobiological events, associated with excessive EtOH drinking, occur within the extended amygdala (E-AMYG); (b) the use of excessive drinking procedures, outlined below, in alcohol-preferring, P, and high alcohol-drinking, HAD-1 and HAD-2 rats enables the detection of these events; (c) site-specific lesioning of structures [accumbens-shell (ACBsh), central amygdala (Ce-AMYG), and bed nucleus of the stria terminalis (BNST)], within the E-AMYG, alter the development and/or maintenance of excessive drinking; and (d) experience with these excessive drinking procedures, by P and HAD rats, results in behavioral and/or physiological alterations associated with criteria for a valid animal model of alcoholism (i.e., expression of intoxication, tolerance, and withdrawal signs, and changes in the amount of ethanol consumed and/or pattern of ethanol consumption). Excessive drinking is defined as repeatable and sustainable blood EtOH concentrations (BECs) in the range of 100 to 150 mg% or higher over a chronic period. Three protocols of excessive drinking induction will be used to reflect (a) binge-like drinking during the dark cycle [drinking-in-the-dark-multiple scheduled access (DIDMSA)], with rats receiving three 1-hr access periods spaced 2 hrs apart across the dark cycle; (b) dependence-induced excessive drinking using a prolonged repeated alcohol deprivation (PRAD) procedure, with rats receiving 6 weeks of initial EtOH access followed by multiple cycles of 2 weeks of deprivation from and 2 weeks of re-exposure to EtOH access; and (c) withdrawal-induced, via EtOH vapor inhalation, (excessive) drinking, with a 3 bottle-choice test procedure (WID-3BC) used to measure intake after each cycle of exposure to and withdrawal from EtOH vapor inhalation. Overall, the results of this project will provide valuable information on the complex molecular neurobiological changes that contribute to the development and consequences of excessive alcohol drinking, and aid in the development of interventions for the prevention, and/or treatment of alcohol abuse and alcoholism.