A primate model of cocaine-base smoking has been established that allows rhesus monkeys to smoke in an unrestricted setting. Precise doses of cocaine-base can be delivered, and cardiovascular effects can be continuously monitored by a telemetric device. Initial results established that smoked cocaine-base functions as a potent reinforcer and that bioavailability measures and cardiovascular effects are comparable to those reported in human cocaine-base smoking studies. The purpose of the proposed research is to continue this work with particular emphasis on 1) applying behavioral and pharmacological strategies to reduce cocaine-base smoking, and 2) to establish models of withdrawal and relapse and to examine how behavioral and pharmacological treatments modify these behaviors. Three series of studies are proposed. In the first series behavioral and pharmacological treatment of cocaine-base smoking will be studied. Drugs such as sertraline, a serotonin uptake blocker, and buprenorphine, an opiate mixed agonist-antagonist, will be investigated. Environmental enrichment will be implemented by providing access to drug (ethanol) and nondrug (saccharin) nondrug reinforcers and by varying the economic conditions (cost) of cocaine and the alternative. In addition, the combined effects of drug treatment and the enriched environment will be compared to the effect of each treatment alone. In the second series a model of withdrawal from cocaine-base smoking will be established. Disruptions in food-maintained operant behavior produced by cocaine withdrawal will be modified by changing the cost of cocaine and food. An attempt to effect treatment of the behavioral disruptions will be made by enriching the environment with a nondrug alternative reinforcer (saccharin), and by pretreating with sertraline and buprenorphine. The combined effects of behavioral and pharmacological alterations will be compared to each treatment alone. The third series will establish a model of relapse that has been successfully used with rats and human subjects and other drugs. Priming exposures of cocaine, lidocaine and the treatment drugs, sertraline and buprenorphine will be tested for their potential to reinstate cocaine-trained responding. The cocaine-induced reinstatement of cocaine-trained behavior will be compared with and without environmental enrichment (a nondrug alternative reinforcer; food, saccharin). Visual stimuli associated with cocaine, food and saccharin will be tested for their effects on reinstatement of cocaine-trained responding. These studies will provide valuable primate models for testing behavioral and pharmacological strategies for reducing abuse of smoked cocaine-base.
