Multi-disciplinary methods of cellular neurobiology will be used to determine the brain circuitry and functional properties of brain endorphin and enkephalin peptides and their role in neurophysiological and behavioral phenomena. Immunocytochemical studies, together with lesions, manipulations of axoplasmic transport, and retrograde axonal transport will be employed to define endorphin peptide circuits in avian, rodent and primate brain and in invertebrate nervous systems. Radio-immunoassays, immunocytochemistry, explant cell culture, and in vitro brain slices will be used to characterize points of presumptive endorphinergic transmission by electrophysiological methods of extracellular recording, interacellular recording, micro-iontophoresis and micro-pressure adimistration of peptides and related drugs. Electroencephalography will be employed to examine the pharmacology, receptor specificity, and transmitter interactions underlying the basis of epileptiform limbic seizure produced by injection of endorphin peptides into cerebrospinal fluid. Experiments in awake unrestrained normal or morphine-dependent animals will determine the role of specific endorphin- or enkephalin peptide-mediated circuits in responsiveness to noxious stimuli, and in control of specific hypothalamic and thalamic functions including general somatic sensitivity, body temperature, feeding, drinking, affective components of animal responses, and in general behavioral mechanisms. Chronic implanted stimulating electrodes will be used to simulate human models of endorphin-mediated pain suppression. By defining how and where endogenous opiate peptides function normally, and by determining their characteristic receptor mechanisms, these experiments will help to provide fundamental details of how opiates act to reduce pain and how opioid peptide-mediated cellular mechanisms are altered by phenomena of narcotic abuse.