The major aim of this project is an examination of protein synthesis in rat brain under the influence of narcotic analgesic drugs from several aspects. Two important modulator enzymes, tyrosine hydroxylase and adenyl cyclase, have already been found to increase inactivity during the development of tolerance to morphine. Whether new protein, or increased amounts of protein already present, is synthesized in synaptic membranes of discrete brain areas during the development of tolerance to morphine will be examined by the use of radiolabeled amino acids as protein precursors, and gel electrophoresis as a means of separating membrane proteins into component fractions. The identification of pre-synaptic or post-synaptic membranes as the site of opiate action will be studied by examining the effect of opiates on pre- synaptic events (i.e. the release of acetylcholine upon stimulation) and post-synaptic event (i.e. dopamine-induced increases in adenyl cyclase activity).