MECHANISMS OF INCREASED COCAINE SELF-ADMINISTRATION

滥用麻醉品仍然是一个主要的社会和医疗问题， 美国的据报道，有2到3百万的慢性 可卡因使用者，可卡因使用是一个持续的公共卫生问题。 同时酒精依赖发生在62%至94%的慢性可卡因 用户.从可卡因和乙醇滥用共病中获得的信息。 可卡因和乙醇组合的自我管理具有特殊的 重要性有显著的神经化学，生理， 行为和治疗相关的相互作用，当可卡因和乙醇 同时给予。与人用药物相关的一个关键问题 滥用是为了确定是否同时可卡因和乙醇自我- 给药比单独使用任何一种药物具有更大的滥用潜力。 单药和多药联合给药的自我给药将 在四只恒河猴身上做了实验。两种方法显示出预测性 评估滥用可能性的效用。在实验1中，猴子会 在0.4 mg/ml可卡因、8%乙醇、载体和 这两种药物的组合。在实验2中，猴子会对 在届会期间的条件下， 成本的增加（即，累进比率）。这两种程序 将严格检验可卡因乙醇 组合比成分具有更大的奖励效应， 车辆两个，几个，机制，可以解释， 在同时使用可卡因和乙醇时观察到的相互作用 1）乙醇可以“掩盖”可卡因的味道，导致 增加摄入量和2）肝脏生产的古柯乙烯，第三 精神活性物质，可能会增加整体增强效果。 实验3检验了对可卡因的偏好和 乙醇是基于味道，用糖精代替乙醇， 完成如实验1中的选择程序。在实验4中， 猴子将自我施用药物组合， 绘制，以便可以测量可卡因血浆浓度。这 信息是必要的，以支持假设， 在可卡因和乙醇的相互作用中起作用。成熟的 所提供的方法是检查 临床相关假设。这个应用程序的一个重要方面 是直接关注药物滥用的临床相关问题。

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.