18. GOALS FOR FELLOWSHIP TRAINING AND CAREER The fundamental goal I hope to achieve through this fellowship training is to understand the tasks involved in postulating a scientific question. Through my training, I hope to learn how to formulate good hypotheses, design valid experiments to test these hypotheses, become skilled at new techniques, and express my results in a coherent and intelligible manner, both written and verbally. My chosen sponsor is qualified to train me in these areas, as he has many years of experience in conducting his own research and guiding students. I hope to integrate the information I learn through this training with my medical knowledge to pursue a career in academic medicine. I plan to combine clinical practice with scientific research and teaching, and this MD/PhD training program will better enable me to achieve these goals. SPONSOR 19. NAME AND DEGREE(S) Richard E. Harlan. PhD 20. POSITION/RANK Professor 21. RESEARCH INTERESTS/AREAS Neurobiology of Substance Abuse RESEARCH PROPOSAL 22. DE^ devastating problems our country faces today. Despite extensive research, many difficulties in treating drug abuse stem from the limited knowledge of the brain circuitry involved in the addiction pathway. The target system for the proposed research involves a morphine activated serotonergic pathway. Morphine binds to u-opioid receptors located on the dendrites of GABAergic interneurons of the dorsal raphe nucleus (DR). These GABAergic neurons synapse onto serotonergic neurons of the DR that project to neurons of the striatum and cortex. It is thought that morphine-induced release of serotonin in the striatum and cortex will induce the translocation of the (311 isoform of protein kinase C (PKC).
The specific aims of this project are to (a) block the binding of morphine to the u-opioid receptors in the DR, (b) block the binding of 5HT to the 5HT2A/2C receptors in the striatum and cortex, and (c) activate the GABAA receptors on the serotonergic neurons of the DR, aj.1to inhibit translocation of PKC3II in the striatum and cortex. The techniques of stereotaxic surgery, chronic cannulation, immunocytochemistry, immunoblotting, and fluorescence deconvolution microscopy will be used to obtain the necessary data. The proposed xperiments will solidify the structure of this hypothesized circuit and will bring the field one step closer to understanding the phenomenon of drug abuse. PHS 416-1 (Rev.12/98^ Form Pane 2 RR cc NAME (Last, first, middle initial) Individual NRSA Application Kailas, Sudha R. Table of Contents ========================================Section End===========================================
