MECHANISMS OF INCREASED COCAINE SELF-ADMINISTRATION

可卡因滥用仍然是#年的一个主要社会和医疗问题。 美国。据报道，有200万到300万慢性 可卡因吸毒者，可卡因的使用是一个持续的公共卫生问题。 62%至94%的慢性可卡因同时存在酒精依赖 用户。从可卡因和酒精并存的滥用中获得的信息。 可卡因和乙醇混合物的自我给药是特殊的 重要性。有重要的神经化学，生理学， 可卡因和酒精时与行为和治疗相关的相互作用 是同时给药的。与人类药物相关的一个关键问题 滥用是为了确定同时存在的可卡因和乙醇是否自身 政府比任何一种药物都有更大的滥用潜力。 单药和多药联合的自我给药将是 在四只恒河猴身上进行了检查。有两种方法显示出了预测性 在评估滥用潜力方面的效用。在实验1中，猴子会 在0.4毫克/毫升的可卡因、8%的乙醇、交通工具和 两种药物的组合。在实验2中，猴子会对 在会议期间的条件下，上述相同的解决方案 成本增加(即累进比率)。这两个过程 会严格测试可卡因-乙醇的假设 组合的回报效果比成分或 车辆。几种机制中的两种，可以解释 可卡因和乙醇同时使用时观察到的相互作用 给药方法：1)乙醇可能会“掩盖”可卡因的味道，导致 增加摄入量和2)肝脏产生可可乙烯，三分之一 精神活性物质，可增加整体强化效果。 实验3检验了对可卡因的偏好和 乙醇是以味道为基础的，用糖精代替乙醇， 完成实验1中的选择程序。在实验4中， 猴子将自行给药，血液将被 绘制，以便可以测量可可乙烯血浆浓度。这 信息是必要的，以支持可可乙烯的假设 在可卡因和乙醇的相互作用中起作用。久负盛名 提供的方法是检查 临床相关假说。此应用程序的一个重要方面 是它直接关注与临床相关的药物滥用问题。

Cocaine abuse continues to be a major social and medical problem in the United States. With reports that there are 2 to 3 million chronic cocaine users, cocaine use is a continuing public health problem . Concurrent alcohol dependence occurs in 62 to 94% of chronic cocaine users. Information gained from comorbid cocaine and ethanol abuse. Self-administration of a cocaine and ethanol combination is of special importance. There are significant neurochemical, physiological, behavioral and treatment related interactions when cocaine and ethanol are concurrently administered. A key concern relevant to human drug abuse is to determine if concurrent cocaine and ethanol self- administration has greater abuse potential than either drug alone. Self-administration of single and polydrug combinations will be examined in four rhesus monkeys. Two methods have shown predictive utility in assessing abuse potential. In experiment 1, monkeys will have a choice among pairs of 0.4 mg/ml cocaine, 8% ethanol, vehicle and a combination of both drugs. In experiment 2, monkeys will respond for the same solutions listed above under conditions of within session increases in cost (i.e., progressive-ratio). Both of these procedures will rigorously test the hypothesis that the cocaine-ethanol combination has greater rewarding effects than the constituents or vehicle. Two, of several, mechanisms which may account for the interactions observed during concurrent cocaine and ethanol self- administration are 1) ethanol may "mask" cocaine's taste leading to increased intake and 2) liver production of cocaethylene, a third psychoactive substance, may increase the overall reinforcing effect. Experiment 3 tests the hypothesis that preference for cocaine and ethanol is based on taste by substituting saccharin for ethanol and completing a choice procedure as in Experiment 1. In Experiment 4, monkeys will self-administer the drug combination and blood will be drawn so that cocaethylene plasma concentrations can be measured. This information is necessary to support the hypothesis that cocaethylene plays a role in cocaine-ethanol interactions. The well established methods provided are excellent vehicle by which to examine the clinically relevant hypothesis. An important aspect of this application is its direct focus on clinically pertinent issues of drug abuse.