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。具体来说，长期服用d-安非他明、莫达非尼和托莫西汀将被研究。6只恒河猴将作为实验对象。出于几个原因，将使用口服途径。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。大多数关于可卡因自我给药的药物效应的研究都使用了静脉注射途径；然而，重要的是确定通过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。在所有的研究中，治疗药物将长期使用。第一和第二项研究将使用FR和PR时间表，因为这是静脉注射可卡因实验中最常用的时间表。衡量药物效应的一种方法是PR计划下的反应率与FR计划下的反应率之比。在这两项研究中，药物效应还将研究药物强化行为的恢复和消失以及行为的维持。第三项研究将采用将“寻求毒品”和“毒品消费”分开的设计。因此，在初始组件（Interlock计划FR 480， FI30分钟计划）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作用的选择性。可卡因和一种同样增强作用的糖精溶液将在非独立的可变比率表下同时供应。这些时间表产生了反应模式，导致同时摄入两种强化物

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.