Rat Animal Models Core (RAMC)

描述（由申请方提供）：大鼠动物模型核心（RAMC）的长期目标是更好地了解过量乙醇（EtOH）饮用的发展和维持背后的分子神经生物学事件，以及这些神经生物学事件如何促成过量EtOH饮用的长期后果。待检验的总体假设是：（a）扩展杏仁核（E-AMYG）内发生了许多与过量饮酒相关的神经生物学事件;（B）使用过量饮酒程序，如下所述，在偏爱酒精的P和大量饮酒的HAD-1和HAD-2大鼠中能够检测到这些事件;（c）E-AMYG内结构[杏仁核壳（ACBsh）、中央杏仁核（Ce-AMYG）和终纹床核（BNST）]的位点特异性损伤改变过量饮酒的发展和/或维持;和（d）P和HAD大鼠的这些过量饮酒过程的经历导致与有效的酒精中毒动物模型的标准相关的行为和/或生理改变（即，中毒、耐受和戒断症状的表达，以及乙醇消耗量和/或乙醇消耗模式的变化）。过量饮酒被定义为可重复和可持续的血液乙醇浓度（BEC）在100至150 mg%或更高的范围内。将使用三种过量饮酒诱导方案来反映（a）在黑暗周期期间的暴饮暴食[在黑暗中多次预定的饮酒（DIDMSA）]，其中大鼠在整个黑暗周期中接受间隔2小时的三个1小时的访问期;（B）使用延长的重复酒精剥夺（PRAD）程序的依赖性诱导的过量饮酒，大鼠接受6周的初始EtOH接触，随后是2周的剥夺和2周的重新暴露于EtOH接触的多个循环;和（c）通过EtOH蒸汽吸入引起的戒断，（过量）饮酒，使用3瓶选择测试程序（WID-3BC），用于测量每次暴露于EtOH蒸汽吸入和从EtOH蒸汽吸入中撤出后的摄入量。总体而言，该项目的结果将提供有关复杂分子神经生物学变化的宝贵信息，这些变化有助于过度饮酒的发展和后果，并有助于制定预防和/或治疗酒精滥用和酒精中毒的干预措施。

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.