DRUG EFFECTS ON ORAL COCAINE-REINFORCED BEHAVIOR

将研究药物对口服可卡因自我给药的影响。具体而言，将研究d-苯丙胺、莫达非尼和托莫西汀的长期给药。六只恒河猴将作为受试者。将使用口服途径有几个原因。可卡因被口服滥用，重要的是，通过口服途径摄入可卡因与通过鼻内途径摄入可卡因相似。大多数药物对可卡因自我给药的影响研究都使用了静脉注射途径;然而，重要的是要确定静脉注射途径获得的结果是否可以扩展到其他途径。将进行四项研究。在所有研究中，治疗药物将长期给药。第一项和第二项研究将使用FR和PR时间表，因为这些是静脉注射可卡因实验中最常用的时间表。药物效应的一个指标是PR方案下的缓解率与FR方案下的缓解率之比。在这两项研究中，还将检查药物对药物强化行为的恢复和消退以及对行为维持的影响。第三项研究将采用一种将"寻求毒品"和"消费毒品"分开的设计。“因此，在最初的组成部分（联锁计划FR 480，FI 30分钟计划），药物对行为的影响可以在体内没有可卡因的情况下进行评估。第四项研究涉及药物作用的选择性。在非独立的可变比率计划下，可同时提供复方制剂和同等强化的糖精溶液。这些时间表会产生反应模式，导致体内同时摄入两种强化剂 相同的时间段。重要的是，时间表允许分配给每个验证者的响应分布的变化，而不必减少获得的验证者的总数。拟议研究的结果将检查早期人类和猴子研究结果的普遍性，即d-安非他明减少可卡因摄入量，这些研究将确定使用目前批准用于人类的激动剂类药物的可行性。

The effects of medications on oral cocaine self-administration will be investigated. Specifically, chronic administration of d-amphetamine, modafinil, and atomoxetine will be studied. Six rhesus monkeys will serve as subjects. The oral route will be used for several reasons. Cocaine is abused orally, and importantly intake of cocaine via the oral route is similar to intake of cocaine via the intranasal route. Most studies of drug effects on cocaine self-administration have used the i.v. route; however, it is important to determine if findings obtained with the i.v. route can be extended to other routes. Four studies will be conducted. In all studies treatment drugs will be administered chronically. The first and second studies will use FR and PR schedules, for these have been the most commonly used schedules in i.v. cocaine experiments. One measure of drug effects will be the ratio of responses under the PR schedule to the ratio of responses under the FR schedule. In these two studies drug effects will also be examined on the resumption and extinction of drug reinforced behavior as well as on the maintenance of behavior. The third study will employ a design that separates "drug seeking" and "drug consumption." Thus, in the initial component (an Interlock schedule FR 480, FI30 min schedule), medication effects on behavior can be assessed in the absence of cocaine in the body. The fourth study concerns the selectivity of medication effects. Cocaine and an equally reinforcing saccharin solution will be concurrently available under non independent Variable-Ratio schedules. These schedules generate patterns of responding that result in the concurrent intake of both reinforcers within the same time segments. Importantly the schedules permit variations in the distribution of responding allocated to each reinforcer without necessarily decreasing the total number of reinforcers obtained. The results of the proposed studies will examine the generality of earlier findings with humans and monkeys that d-amphetamine decreases cocaine intake, and the studies will determine the feasibility of using agonist type medications that are currently approved for use in humans.