This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The progression of drug addiction in humans typically involves a transition from casual, recreational drug use to compulsive drug use that leads to serious adverse consequences. Hence, the frequency and pattern of drug use changes as a function of drug history. This is a project in its third year to utilize i.v. drug self-administration protocols in rhesus monkeys to identify critical behavioral endpoints indicative of transitional states in drug addiction. Efforts have focused on behavioral training with i.v. drug self-administration protocols. This phase of the project has provided drug exposure on a limited access procedure to model recreational drug use. A total of four subjects have completed the behavioral protocols and six additional subjects have been acclimated to the restraint chairs and testing apparatus. Reinstatement of drug-seeking behavior by cocaine priming injections and drug-paired stimuli has provided another objective behavioral measure indicative of transitional states in drug use. Parallel studies have been initiated with in vivo microdialysis in awake subjects to characterize functional changes in monoamine neurochemistry associated with the behavioral changes observed. Brain tissue obtained at different transitional states will be assayed for gene expression profiles and protein products to provide relevant molecular markers to complement behavioral measures. Brain tissue obtained from control subjects and three pilot animals exposed to cocaine has been characterized for gene expression profiles that will provide critical information regarding long-term effects of drug exposure. Studies proposed in the coming year will compare behavioral and molecular markers in subjects with a more extensive history of cocaine use.
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