The goal is to investigate the effects of opioids on neuroendocrine function in developing rats. The rationale is based on clinical finding of disrupted growth and CNS development following perinatal opiate addiction, and the growing evidence that endogenous opioids are important regulators of normal neuroendocrine ontogeny. Opioid effects on reproductive development will be studied. Endogenous opioids are thought to contribute to pubertal development, and so this system is a primary target, and a good model for studying perinatal opioid effects. Opioid agonist treatments should retard, and antagonists accelerate puberty. Vaginal opening, the establishment of normal estrus cycles and preputial separation will be followed after treatment with the opioid agonist methadone or the antagonist naltrexone. Serum levels of LH, estradiol, testosterone, hypothalomoc LHRH, pituitary LH and hypothalamic norepinephrne turnover will be measured to investigate specific mechanisms. The second major goal is to characterize further the dual neural control of opioid-induced prolactin (PRL) secretion. We have shown that opioid-induce induced PRL secretion changes from a serotonin (5HT)-independent to a 5HT-dependent process during ontogeny. Effects of dopamine (DA) and opioid drugs on hormone secretion and studies of 5HT and DA turnover will be used to identify specific mechanisms mediating these two responses. Finally, the role of different opioid receptor subtypes in neuroendocrine regulation will be defined further, with an emphasis on delineating the ontogeny of receptor subtype-specific GH, PRL, LH, ACTH, and TSH responses, and the differential development of tolerance at these receptors. These studies should provide insight into normal and disrupted function of endogenous opioid systems, which appear to supply a """"""""primitive"""""""" control of hormone secretion before other neural controls mature. These studies have clinical relevance for the considerable population of women who are exposed to opiates through drug abuse or through physiologically-induced secretion association with activities like excessive exercise.
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