This application is in response to PA-95-049 for the Mentored Research Scientist Development Award. This award will allow the candidate, a NIDA-trained pharmacologist and neuroanatomist, to pursue an additional period of training in the fundamentals of magnetic resonance imaging and spectroscopy. The immediate goals of the training and research periods are to provide intensive instruction in the fundamentals of magnetic resonance (MR), on advanced topics in MR, on cutting edge applications including magnetic resonance spectroscopic imaging (MRSI), and on the operation of a clinical scanner, so that the applicant achieves competency in all areas of MR experimentation. The intermediate-term goal of this proposal is to utilize cutting edge techniques, which will be introduced to the applicant by the mentor and consultant, to examine the effects of psychomotor stimulant administration on brain function. Under the supervision of the Mentor, Dr. Renshaw, studies of cerebral metabolism using proton (1H) and phosphorus (31P) magnetic resonance spectroscopic imaging (MRSI) will be conducted at baseline and following intravenous methylphenidate administration. Studies of regional cerebral proton and phosphorus metabolites will be accomplished with MRSI, which was introduced to the performance site by the Consultant, Dr. Wald. These techniques are exceptionally well-suited for the study of stimulant effects on human brain function because they are noninvasive and have excellent spatial and temporal resolution. Methylphenidate challenge studies will be conducted in control subjects and in subjects with a self-reported history of casual cocaine use, in order to compare cerebral metabolic responses in naive and stimulant-experienced populations. Stimulant challenges will be conducted in a double-blind, placebo-controlled manner. These studies will help to determine the acute effects of stimulant challenge on human cerebral metabolism, whether gender differences exist in the effects of methylphenidate on these functions, and whether naive subjects differentially respond to stimulant challenge as compared to experienced subjects. In addition to providing potential insights into mechanisms of stimulant alteration of brain function and induction of brain dysfunction, the present training and hands-on research experience will allow the applicant to meet his long term goal to become a fundamentally sound researcher in the application of MR to the study of substance abuse.
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