This research project consists of experiments that are designed to study the ability of exogenous opioids to regulate the stimulated release of an endogenous opioid, methionine-enkephalin (enkephalin). Recently, it has been demonstrated that exogenous opioids regulate the evoked release while higher concentrations inhibit release. The major question to be examined is whether the ability of low doses of opioid to enhance the stimulated release of enkephalin is due to the activation of a biochemical pathway that is different from the pathway that mediates opioid inhibition of enkephalin release. The identification of factors that determine the relative responsiveness to the excitatory and inhibitory effects of opioids will be investigated. Results from these experiments might be of importance in understanding the physiological mechanisms that underline opiate tolerance and dependence.