There is increasing evidence that growth factors and neuropeptides, including opioids, play an important role in embryonic development. Opioid peptides and receptors show temporal and spatial distribution that are consistent with growth related effects. In the central nervous system, opioid receptors are found not only on neurons but also on astrocytes, oligodendrocytes and microglia. Despite some indications that these receptors modulate glial function, very little information exists concerning the binding parameters of opioid receptors as well as the signal transduction pathways employed by these proteins. In addition, there is a paucity of data concerning the effects of chronic opiate exposure on glial cellular function or whether tolerance develops in response to chronic administration of opiates. Considering that glial cells are critical to neuronal survival and function, any alterations in glial cells could have deleterious consequences on normal brain development and neuronal plasticity. Therefore, the objectives of this proposal are to (1) determine the binding characteristics (Bmax and Kd) of glial opioid receptors, (2) identify signal transduction pathways utilized by these receptors, (3) determine if prolonged exposure to opioid receptor agonists induces tolerance and finally (4) determine if chronic opioid administration alters the function and development of glial cells. The clinical significance of this research is two-fold: (1) it provides a model to study longterm effects of opioids on neuroglia development, which is an area neglected in both basic science and clinical settings and (2) provides information regarding the possible ramifications of in utero exposure to opiates in infants born to heroin-addicted mothers.