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量乙醇（EtOH）饮酒发展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量乙醇饮酒的长期后果。要测试的总体假设是：(a)与过量饮用EtOH相关的许多神经生物学事件发生在扩展杏仁核（E-AMYG）内；(b)在嗜酒型、P型和高酒精型、hd -1型和hd -2型大鼠中使用如下所述的过量饮酒程序，可以检测到这些事件；(c) E-AMYG内的结构[伏隔壳（ACBsh），中央杏仁核（Ce-AMYG）和终纹床核（BNST）]的部位特异性病变改变了过度饮酒的发展和/或维持；(d) P和HAD大鼠在这些过量饮酒过程中的经验，导致与酒精中毒动物模型标准相关的行为和/或生理改变（即，中毒的表现、耐受性和戒断迹象，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EtOH浓度（BECs）在100至150mg %或更高的慢性时期。过量饮酒诱导的三种方案将被用来反映(a)在黑暗周期中狂欢式饮酒[在黑暗中饮酒的多重预定访问（DIDMSA）]，大鼠在黑暗周期中接受三个间隔2小时的1小时访问期；(b)使用长时间重复酒精剥夺（PRAD）程序诱导依赖性过度饮酒，大鼠接受6周的初始EtOH，然后是2周的EtOH剥夺和2周的EtOH重新暴露的多个周期；(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（widd - 3bc）来测量每个周期暴露于EtOH蒸汽吸入和戒断后的摄入量。总的来说，该项目的结果将提供有关导致过度饮酒的发展和后果的复杂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.