This is a request for an NIDA Scientist Development Award (K21) entitled """"""""FMRI Studies of Brain Reward and Emotion"""""""", and is submitted in response to a NIDA notice of """"""""special research scientist development awards for fiscal year 1995."""""""" The Candidate's primary interest is in the study of brain mechanisms mediating human motivation and emotion, particularly in relation to the development of substance abuse and dependence with cocaine or opiates. By focusing on the neurobiology of drug-induced reward, and on the subsequent emotional memory which might encourage repeated drug use, the proposed research should have important implications for clinical treatment of drug abuse. Substance abuse research consolidates the Candidate's interests and training in psychiatry, clinical pharmacology, and functional magnetic resonance imaging (fMRI) on clinically relevant questions. Through this proposal, the Candidate seeks to gain training in (1) the human neurobiology of cocaine and opiate abuse, (2) the neuroscience of brain reward and emotion, (3) the implementation of experimental psychology and cognitive neuroscience paradigms, and (4) the advanced use of fMRI to probe fundamental questions regarding drug euphoria/dysphoria and memory of that euphoria/dysphoria. To further the Candidate's understanding of fMRI, he is also requesting training in permutation based statistical methods of data analysis. The research project designed to complement this training program involves the use of drug infusions and psychological paradigms with fMRI to study how a circuit comprising the ventral tegmental area (VTA), nucleus accumbens (NA) and amygdala function during human drug induced euphoria, and memory of that euphoria. The circuitry between the VTA, NA and amygdala represent the crossroads of the systems for brain reward and emotional memory as studied in animal models. This project seeks to study in humans the interaction between these systems which may drive repeated substance use. Specifically: (A) The effects of cocaine and morphine on VTA, NA and amygdala function will be compared and correlated with drug kinetics, cardiovascular effects and euphoria in dependent and nondependent abusers of each substance. (B) Normal controls along with dependent and nondependent abusers of each drug will be studied with fMRI and psychological paradigms specific to reward and emotional memory function. These experiments will seek to answer how the state of drug dependency alters normal VTA, NA and amygdala function. (C) Lastly, operant conditioning paradigms using cocaine and morphine as the rewards with substance abusers will address whether the circuitry of emotional memory works differently during drug induction of emotion than during emotions aroused by cognitive paradigms. This research will be integrated with the training to foster the Candidate's development as a productive independent investigator committed to the study of brain mechanisms underlying human motivation and emotion and their contribution to addiction.
