Drug abuse has been identified as a significant exacerbating factor in promoting the development of AIDS. The long-term goal of our research is to investigate the underlying mechanism of the effect of drugs such as opioids on attenuating host immune function. Preliminary studies on the molecular basis of the opioid effect on the progression of AIDS have led to our discovery of the expression of brain-like opioid receptors on lymphocytes, the cells of the immune system. The purpose of this proposal is to further characterize these receptors and study the factors involved in the regulation of lymphocyte opioid receptors.
The specific aims of this research are (l) to determine the effect of chronic morphine and methadone administration on the expression of opioid receptors in monkey lymphocytes in vivo and in vitro, (2) to determine the effect of morphine, methadone and dynorphin treatment on the expression of opioid receptors using the CEM x174 cell line, a human T and B hybrid cell line susceptible to SIV infection, and (3) to determine the effect of opiate treatment on cytokine production and the G-protein-coupled signalling pathway of immune cells (monkey lymphocytes and CEM x174 cells). Methods to be used include the identification of receptor binding sites on immune cells in correlation with the presence of receptor mRNA, quantitative assays of cytokine release and protein kinase C/phospholipase C activity, and measurements of the up/down regulation of lymphocyte opioid receptors as influenced by SIV viremia after morphine, methadone or dynorphin treatment. Data obtained from this study will provide significant information toward our understanding of the relationship between opioid abuse and the complex brain immune axis, and this study may lead to the development of new therapeutic and prophylactic strategies in controlling AIDS and AIDS-related diseases.
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