The goal of the proposed research is to elucidate the behavioral and biochemical mechanisms subserving plasticity of endogenous opioid systems in the developing animal. In particular, the mechanisms underlying receptor regulation and peptide changes following chronic administration of narcotic agonist (morphine) and antagonist (naltrexone) will be pursued. Receptor density changes for specific opiate receptor types following long-term in vivo administration of 1) morphine and 2) naltrexone will be examined in 1) the offspring of treated pregnant rats and 2) pups at various ages after birth. In the second project, the precise neuroanatomical pattern of opiate receptor density changes in the developing animal will be studied using in vitro light microscopy autoradiography in conjunction with 2-deoxyglucose autoradiography. An attempt will be made to correlate patterns of agonist and antagonist-induced opiate receptor regulation with metabolic activities and functional pathways of the brain. The goal of the third project is to determine the possible alterations in brain opioid peptide levels (methionine-enkephalin, Beta-endorphin, dynorphin) following long-term exposure of the developing animal to 1) morphine and 2) naltrexone. These alterations will be correlated with changes in met-enkephalin synthesis in these animals. The goal of the fourth project is to characterize the behavioral consequences of narcotic agonist and antagonist administration in the developing animal using both the tail-flick and fore-paw withdrawal paradigms. These studies are hoped to provide insight into the biochemical and behavioral consequences of long-term in vivo administration of opiate agonists and antagonists on the development of opiate receptors and to correlate these patterns with the more general problem of plasticity in the central nervous system.
