The goals of the proposed research are to define the molecular, neuroanatomical and behavioral mechanisms subserving the regulation of opioid receptors in the developing animal. Specifically, molecular mechanisms underlying receptor and peptide changes following chronic administration of opioid agonist or antagonist in (1) the offspring of treated pregnant rats and (2) pups at various ages after birth will be examined. In vitro autoradiographic studies will allow for direct comparisons of neuroanatomical patterns of opioid receptor regulation with known functional pathways in the brain. This laboratory has demonstrated that chronic agonist and antagonist treatment produce changes in opioid receptor density in neonatal brain. These studies seek to extend these observations to a molecular mechanistic level. Specifically, the following questions will be addressed: 1) Does prenatal exogenous opioid exposure alter peptide levels in offspring? 2) Are the changes in peptide levels the result of altered levels of the corresponding mRNA)? 3) Are opioid peptides and the processing enzymes involved in their synthesis regulated differentially throughout the brain? 4) what are the behavioral consequences of prenatal or postnatal chronic opioid exposure in the developing central nervous system? Together, these studies are expected to provide important new information about the synthesis and regulation of the developing opioid systems as well as the phenomena of opioid tolerance and dependence.
