Alcohol Cues:Opioid Anatagonism/ Behavioral Economics

描述（由申请人提供）： 条件酒精线索产生渴望，并可能有助于复发。酒精暗示的这些影响可能与它们的功能有关：1）条件反射者（他们保持与他们接触的行为），以及2）饮酒的动机（接触他们使饮酒更有可能）。内源性阿片系统介导酒精的强化作用，并与酒精中毒的遗传易感性有关。很少有研究集中在阿片系统的作用，在条件强化和激励效应的酒精线索。我们最近开发了一个程序（观察反应程序），避免了许多问题与其他动物模型的条件强化效应的酒精线索，但尚未检查的动机影响的酒精线索饮酒。该程序用于检查酒精线索的神经药理学机制的效用也是未知的。这项研究有三个具体目标。首先，我们的目标是研究酒精线索在这个过程中的激励作用，通过研究他们的影响，饮酒的敏感性增加的酒精成本。在实验1中，大鼠将在增加的成本（每单位酒精的工作量）中自我管理酒精，并在酒精线索可用或不可用时检查对价格的敏感性。我们的第二个目标是研究阿片拮抗作用如何影响饮酒的敏感性和对酒精提示的反应，以增加酒精的成本。Exp. 2检验了纳洛酮对饮酒和在观察-反应程序中对酒精线索的反应的影响。第三个目的是确定纳洛酮的作用是否与条件酒精线索的可用性相互作用。Exp. 3检查这种相互作用的一个子集的价格和纳洛酮剂量确定在实验1和实验。2.这项实验将确定阿片拮抗作用产生的酒精消耗量的任何减少是否受到酒精线索的激励作用的影响。这些方法的进一步发展和评估对于我们理解酒精线索及其在渴望和复发中的作用的持续增长非常重要。通过使用观察-反应程序，我们可能能够更好地减少他们对正在接受酒精中毒治疗的人的影响。未来的研究可能会检查特定阿片受体亚型或其他受体系统在酒精提示效应中的作用，以及它们与酒精中毒遗传易感性的关系。

DESCRIPTION (provided by applicant): Conditioned alcohol cues produce craving and may contribute to relapse. These effects of alcohol cues may be related to their functioning as: 1) conditioned reinforcers [they maintain behavior that produces contact with them], and 2) motivators of drinking [contacting them makes drinking more likely]. The endogenous opioid system mediates the reinforcing effects of alcohol and is related to genetic susceptibilities to alcoholism. Little research has focused on the role of the opioid system in the conditioned reinforcing and motivating effects of alcohol cues. We recently developed a procedure (the observing-response procedure) that avoids many problems with other animal models of the conditioned reinforcing effects of alcohol cues, but have not yet examined the motivational impact of the alcohol cues on drinking. The utility of this procedure for examining the neuropharmacological mechanisms of alcohol cues is also unknown. This research has three specific aims. First, we aim to examine the motivating effects of the alcohol cues in the this procedure by examining their impact on the sensitivity of alcohol drinking to increases in the cost of alcohol. In Exp.1 rats will self-administer alcohol across increasing costs (work per unit alcohol) and sensitivity to price will be examined when alcohol cues are available or unavailable. Our second aim is to examine how opioid antagonism affects sensitivity of drinking and responding for alcohol cues to increases in the cost of alcohol. Exp. 2 examines the effects of naltrexone on drinking and responding for alcohol cues in the observing-response procedure. The third aim is to determine if the effects of naltrexone interact with availability of conditioned alcohol cues. Exp. 3 examines this interaction with a subset of prices and naltrexone doses determined in Exp.1 and Exp. 2. This experiment will determine if any decreases in alcohol consumption produced by opioid antagonism are affected by the motivating effects of alcohol cues. The further development and evaluation of these methods is important for the continued growth of our understanding of alcohol cues and their role in craving and relapse. By using the observing-response procedure we may be better able to decrease their impact on people being treated for alcoholism. Future studies could examine the role of specific opioid receptor subtypes or other receptor systems in the effects of alcohol cues and their relationship to genetic susceptibility to alcoholism.