This is an renewal application for a ADAMHA Level II Research Scientist Development Award. During the past four years of this award that candidate has spent 85 - 95% of his time engaged in drug abuse research. The unifying theme of the candidate's research goals is the use of a multidisciplinary approach to study reinforcing efficacy, polydrug abuse and potential pharmacotherapies for drug abuse using both human and animal models. Self-administration studies using rhesus monkeys and measures of electrophysiological activity (including topographic mapping) in male and female volunteers will be employed. These long-term plans are both a continuation and an extension of prior parametric studies of the reinforcing properties of various drugs of abuse. The described research plan is based on the candidate's involvement with five currently funded projects and one submitted grant. The proposed clinical studies are aimed at studying the pharmacodynamics of polydrug abuse in various populations of men and women. Drug-induced alterations in electroencephalographic GM activity, event-related potentials, physiological responses, behavioral states, and cognitive function will be studied during acute intoxication. Regional changes in brain electrical activity during intoxication will be quantified using topographic mapping techniques to determine if neurophysiologic changes are correlated with drug-induced subjective and behavioral effects.
Specific aims are directed at determining if such alterations are modified by pretreatment with potential pharmacotherapeutic agents for cocaine abuse. In addition, the issue of vulnerability to drug abuse will be explored by correlating pre-drug control measures of EEG and event-related potentials with the subsequent cocaine- and marihuana--induced responses. The submitted grant is designed to evaluate the use of passive body heating as an alternative to benzodiazepines in elderly insomniacs who might become dependent on sleeping pills. The behavioral pharmacology of buprenorphine, a partial opioid agonist, will be studied in a rhesus monkey self-administration procedure. This research is designed to evaluate the neurobiological aspects of buprenorphine's and related compound's ability to alter the reinforcing properties of cocaine. Data obtained from these experiments will enhance our basic understanding of the nature of the interactions between two drugs of abuse and how this relationship alters drug reinforcement. The candidate has made a strong commitment to research and plans for the next five years of his professional growth include: 1) study the nature of polydrug abuse, 2) develop numerous neuroimaging techniques to quantify drug-induced alterations in brain function, 3) utilize polysomnography to measure subtle changes in low wave sleep during buprenorphine maintenance in drug dependent individuals and 4) continue to refine the primate drug-self-administration model to assess potential pharmacotherapies for drug abuse. The present application is being sought to provide the candidate with continued stability of support essential for his sustained commitment to scientific research in the field of drug abuse and to ensure his continued level of productivity.
