DESCRIPTION: (Applicant's Abstract) This application is in response to PA-95-053 for the Mentored Clinical Scientist Development Award. This award will allow the candidate, a neurologist with additional training in functional neuroimaging and public health, to become expert in the neuroscience of drug abuse and ultimately become an independent investigator. The immediate goal of the candidate is to acquire training in the experimental methodology of applied clinical drug abuse research. Specifically, the candidate hopes to augment neuroimaging skills with a more complete understanding of the neurobiology, neuropharmacology, physiology, and behavioral aspects of addiction and problems in drug abuse. The mentor, Dr. Jack Mendelson, is a unique resource for guiding the candidate in this development program. Besides Dr. Mendelson, the program utilizes the expertise of several preceptors with different skills pertinent to the goals of this application, including neuroimaging (Drs. Renshaw and Cohen), the neuropharmacology of drug abuse (Dr. Lukas), and statistical analysis of functional imaging datasets (Dr. Lange). The research plan that complements this development program focuses on cocaine, a tremendously addictive drug that is neurologically damaging and neuroscientifically intriguing. The research plan details the application of two fMRI techniques, dynamic susceptibility contrast (DSC) and blood oxygenation level dependent (BOLD) imaging, to assess cocaine's acute and chronic effects on brain hemodynamics and function. These techniques are extremely well-suited to the study of drug effect on brain function due to their extraordinary spatial and temporal resolution, ease of repetition, and minimal invasiveness. The specific aims of the research plan are to assess 1) the acute effect of cocaine injection on global and regional relative cerebral blood volume (relCBV) in recreational cocaine users 2) the acute effect of cocaine on brain functional activation, both generally as well within dopaminergic projection areas likely to underlie cocaine's reinforcing effect and 3) the effects of chronic cocaine abuse on global and regional relCBV at rest and in response to cocaine-related cues. The candidate's institution is very committed to both his development and drug abuse research, and has guaranteed the resources necessary to accomplish these objectives. Importantly, this award will allow the candidate to utilize and contribute to existing, funded drug abuse research at the same institution, and will provide a secure salary commitment so that the candidate can devote the next five years to training in applied clinical drug abuse research. It is expected that the results of these investigations will provide important new insights into understanding cocaine's effect on brain hemodynamics and function, which ultimately promises greater understanding of the neural systems subserving euphoria and addiction.