Chronic drug exposures in monkeys: serial MRI studies

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DESCRIPTION (provided by applicant): The aim of this program is to provide protected time to allow me to devote more than 75% of my effort to continue work on 3 interrelated projects. I am a newly independent Principal Investigator on a NIDA R01 (DA 14674) using functional MRI (fMRI) to elucidate mechanisms underlying sex differences in cocaine's acute brain effects. I am a co-Principal Investigator on a subcontract to a NIDA R01 (DA11231, PI: M. Pollack) using phosphorus spectroscopy (31p MRS) to study cerebral metabolism in methadone-maintained opiate dependent subjects. I am a Principal Investigator on a private foundation grant combining a nonhuman primate chronic cocaine self-administration model along with magnetic resonance (MR) technology to study brain structural and functional effects of chronic cocaine exposures. I developed expertise in clinical MR imaging during a K01 award by conducting studies of the acute brain effects of cocaine and methylphenidate. I identified sex differences in cerebrovascular reactivity to cocaine that may be bases for sex differences in chronic cocaine's brain effects. That work led directly to my R01 grant. I also collaborated on studies of chronic cocaine, heroin, and polydrug abusers that led to the subcontract noted above and learned first hand about confounds and limitations of human models. This led me to pursue collaborations and develop funding to conduct prospective MRI, MRS, and fMRI studies of controlled chronic drug exposures using non-human primate models. My primary goals in monkey studies are to identify relationships between cumulative self-administered cocaine dose and brain dysfunction severity (as suggested by human studies) and to determine how acute drug effects lead to chronic drug-induced brain dysfunction. This work is in collaboration with Dr. Linda Porrino at Wake Forest University. The K02 award will allow me stability and flexibility to continue work on these interrelated projects. This stability is particularly important as I apply expertise learned in my Wake Forest collaboration to develop methods and funding to conduct monkey high field MR studies on the McLean Hospital 4.0 Tesla scanner and on a proposed 9.4 Tesla scanner. The protected time offered by the K02 will allow me more time to train and mentor the next generation of scientists interested in conducting these types of interdisciplinary research, and will assist me in making the transition from newly independent to independent investigator.