OPIOID RECEPTORS ON LYMPHOCYTES AND BRAIN

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DESCRIPTION: (Applicant's Abstract) This K05 Senior Scientist Award is to support Dr. Jean M. Bidlack's research activities. The specific aim of this award is to provide Dr. Bidlack with some release time from grant writing, teaching and administrative responsibilities to cover her salary. This award will allow her to devote the majority of her time to research and the training of graduate students and postdoctoral fellows. Dr. Bidlack will expand her research in studying the expression and regulation of opioid receptors on immune cells. Also, she will continue her studies on medications development for the treatment of heroin and cocaine abuse. These goals will be accomplished within the framework of two RO1 grants and three subcontracts from NIDA. Training activities will be supported by a NIDA Training Grant (T32DA07232). The first project (DA04355 and DA09676) is focused on determining which cells from the immune system express mu, delta and kappa opioid receptors. Studies over the past two years have demonstrated the ability to localize the kappa opioid receptor on mixed immune cell populations by the use of an indirect immunofluorescent amplification procedure combined with flow cytometry and the use of cell surface markers. New fluorescent probes will be evaluated to determine if they can be used to localize mu and delta receptors on lymphocytes. A new area of research involves determining if a protein expressed by the human herpes virus 6 and a homolog of the opioid receptor, based on amino acid sequence, is in fact a functional opioid receptor. This protein will be expressed in COS-7 cells; binding and second messenger studies will determine if the protein is a new functional opioid receptor. The second project (DA03742, DA01674 and U19DA11007) involves evaluating new compounds for their potential as candidates for the treatment of drug abuse. The working hypothesis for which we have produced experimental support is that compounds which release dopamine from the nucleus accumbens promote drug-seeking behavior and those which prevent release of this transmitter prevent drug-seeking behavior. It is known that kappa agonists and mu antagonists inhibit dopamine release in the nucleus accumbens. In collaboration with chemists and behaviorists, we will continue our biochemical and behavioral characterization of new compounds, particularly kappa agonists and mu antagonists. Collectively, these projects will provide new information on the localization and function of the multiple opioid receptors on immune cells and on HHV-6. Also, they will advance efforts in developing drugs to treat cocaine and heroin abuse.