Tyr-W-MIF-1, (Tyr-Pro-Trp-Gly-NH2), is a unique brain peptide in that it acts as an opiate agonist in the opiate-naive animal, but can antagonize morphine and other opiates in the opiate-tolerant animal. Tyr-W-MIF-1 binds to the mu opiate receptor as well as its own """"""""anti-opiate"""""""" receptor. The anatomical sites of action of the peptide will be elucidated by three approaches. Brain regions containing a relative abundance of Tyr-W-MIF-1 will be identified by radioimmunoassay and immunocytochemistry, using an antibody generated and characterized in this lab. Tyr-W-MIF-1 anti-opiate receptor sites will also be localized by quantitative receptor autoradiography. Neuronal activation by Tyr-W-MIF-1 will be determined by FOS immunocytochemistry, and will be separated into opiate and non-opiate components by injection with or without naloxone. Because the role of the peptide changes from opiate agonist to opiate antagonist after tolerance to morphine develops, we propose that Tyr-W-MIF-1 concentrations, anti- opiate receptors, and neuronal activation are altered by the development of morphine tolerance. Demonstration that Tyr-W-MIF-1 is a crucial element in the development of morphine tolerance will aid our understanding of the basic mechanisms of the phenomenon, with implications for new therapies for pain and addiction.
