HIPPOCAMPUS CORRELATES OF DRUG ABUSE IN RATS

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DESCRIPTION: (Applicant's Abstract) The research program outlined in this proposal supports the application for renewal of a Research Scientist Award (K05) to Dr. Sam A. Deadwyler, Professor of Physiology, Bowman Gray School of Medicine, Wake Forest University. The objectives of the research over the next 5 years of the award are delineated in the Research Plan and cover three distinct research areas, each supported by a separate individual research grant. The 3 areas include: 1) effects of cannabinoids on hippocampal memory processes, 2) mechanisms of action of cannabinoid receptors, and 3) neurophysiological assessment of cocaine self-administration. These three major areas of research have been under investigation throughout the duration of the last award period. Each of the grants supporting that research has been renewed and is currently active until the year 2000. The overall strategy of the research proposed is to understand at the cellular and molecular level the effects of cannabinoids and cocaine on neural substrates of behavior and cellular function. With respect to cannabinoids, the effects of both the endogenous cannabinoid (CB1) receptor ligand "anandamide" and the exogenous receptor analogs will continue to be assessed with respect to their influence on memory processes mediated via the hippocampus in the rat. In addition, investigations of the chronic effects of these substances are now underway to determine the mechanisms of tolerance and dependence in the cannabinoid system in the brain. The third area of study focuses on the effects of cocaine on neurons located in the nucleus accumbens (NA), an area of the brain believed to be critical for establishing and maintaining reinforced behaviors. Specifically, these studies will continue to investigate the firing patterns of neurons in the NA in animals self-administering cocaine in order to define those conditions under which the drug alters neuronal activity to support addictive behavior. The renewal of this award will allow Dr. Deadwyler to continue to devote maximal effort to the above research objectives, freeing him from other departmental and teaching responsibilities. It will also provide him with the opportunity to expand his research on the above topics to include more advanced techniques and to make visits to other laboratories to arrange collaborations on topics of mutual interest with other well known researchers in the field.