DRUG EFFECTS ON ORAL COCAINE-REINFORCED BEHAVIOR

将调查药物对口服可卡因自我给药的影响。具体地说，将研究长期服用d-苯丙胺、莫达非尼和托莫西汀。六只恒河猴将作为研究对象。出于几个原因，将使用口头途径。可卡因是口头滥用的，重要的是，通过口服途径摄入可卡因类似于通过鼻腔途径摄入可卡因。大多数关于药物对可卡因自我给药影响的研究都采用静脉注射的方法。途径；然而，重要的是要确定是否通过静脉注射获得的结果。路线可以延伸到其他路线。我们会进行四项研究。在所有研究中，治疗药物将被长期给予。第一项和第二项研究将使用FR和PR计划，因为这是静脉注射中最常用的计划。可卡因实验。衡量药物效果的一个指标是PR计划下的应答率与FR计划下的应答率的比率。在这两项研究中，还将考察药物对药物强化行为的恢复和消亡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“毒品消费”分开的设计。因此，在最初的组成部分(联锁时间表FR 480，FI30分钟时间表)中，可以在体内没有可卡因的情况下评估药物对行为的影响。第四项研究涉及药物效果的选择性。可卡因和同样强化的糖精溶液将在非独立可变比率时间表下同时提供。这些时间表产生的反应模式导致同时摄入两种增强剂 相同的时间段。重要的是，时间表允许分配给每个增强剂的响应分布不同，而不一定减少所获得的增强剂的总数。拟议研究的结果将检验早先在人类和猴子身上发现的d-苯丙胺减少可卡因摄入量的一般性，研究将确定使用目前被批准用于人类的激动剂类型药物的可行性。

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.