This is a request for a Research Scientist Development Award (KO2). The candidate has demonstrated a career commitment to the alcohol research area, and this RSDA award will provide him with time and support needed to expand and enhance his research skills and increase the capacity of the candidate for scientific investigation and mentoring. In particular, the RSDA will afford the candidate the opportunity to develop and establish immunological skills which will complement his demonstrated expertise in neuroendocrinology, and make him more well-rounded, competitive, and productive scientist in the alcohol research field. As detailed in the research plan of this application, the candidate intends to apply immunological techniques and approaches to examine the role of opioid peptides m ethanol modulation of the immune system. Alcoholism in humans has been shown to result in an aberrant immune function, resulting in increased infection and diseases. The mechanisms by which ethanol suppresses resistance to infection are unknown but are probably multi variate in origin, involving effects on lymphoid tissues and neuroendocrine hormones. The effect of corticotropin-releasing hormone and corticosterone in the control of ethanol-modulated immune function has been extensively, studied. Although opioid peptides are known to alter lymphoid tissue functions, the role of these peptides in the ethanol- modulated immunity has not been well studied. Preliminary studies suggest that the hypothalamic opioid peptide. Beta-endorphin (B-EP), responds to interleukin-1, which is known to be released following viral or bacterial infections. Furthermore, the B-EP response to IL-I is altered after acute and chronic ethanol challenges. These data led us to hypothesize that B-EP is an additional neuroendocrine hormone-regulating, ethanol-modulated immune function. To test this hypothesis, we propose to determine I) the effects of IL- I on in vivo and in vitro release of hypothalamic B-EP and natural killer (NK) cell activities in alcoholic and non-alcoholic rats: ii) the effects of hypothalamic administration of B-EP or the opiate antagonist, naltrexone, in IL-I induced NK cell activities in alcoholic and non-alcoholic rats: iii) whether the nitric oxide system is involved in ethanol-modulated B-EP response to IL. We anticipate that the data generated from this study will be significant in understanding the immune dysfunction associated with alcoholism and may indicate potential therapeutic uses of the opiate antagonist, naltrexone, in controlling alcohol-induced immune dysfunction. The research skills learned may be incorporated in other aspects of the candidates research progress. For example Flow cytometry analysis procedure may be employed to more directly address apoptotic process and differentiation of fetal B-EP neurons following ethanol that have been identified by the candidate is previous research Thus RSDA award will also greatly contribute to the overall enhancement of the quality and breadth of his research program. This along with his improved ability in mentoring student will greatly enhanced the candidate is professional growth and maturity as a researcher in the- alcohol field.
|Simasko, S M; Boyadjieva, N; De, A et al. (1999) Effect of ethanol on calcium regulation in rat fetal hypothalamic cells in culture. Brain Res 824:89-96|