The overall goal of my research program is to examine the impact of opiate drugs on the hypothalamic-pituitary-gonadal axis and the possible role of endogenous opioid peptides in regulating activity in this axis. We plan to systematically examine the influence of opiates on testicular steroidogenesis and will attempt to definitively establish that opiates exert their primary effect on the hypothalamic-pituitary-gonadal axis by depressing the hypothalamically-mediated release of luteinizing hormone-releasing hormone (LH-RH). The possible role of endogenous opioids in regulating the hypothalamic-pituitary-LH axis will be approached in three major ways: first, to provide further baseline information concerning whether or not endogenous opioid peptide containing neuronal elements are involved in the activity of the axis; second, to identify the endogenous opioid peptide involved in LH-RH release; and, third, to assess the physiological significance and plasticity of these systems. A final goal of the proposed work will be to examine the long-term consequences of opiate-induced perturbations in the hormone secretions of the hypothalamic-pituitary-gonadal axis, particularly with respect to the development of tolerance and physical dependence. These studies should be significant for three reasons: first, to better define the actions of narcotic drugs on reproductive endocrinology and function in the male; second, to elucidate the opioid peptides mediating the release of LH; and, finally, to elucidate possible biochemical/endocrinological mechanisms involved in the development of tolerance to and physical dependence on the opiates and their complex biochemical and pharmacological interactions with other commonly abused sedative-hypnotic drugs.
