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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30DA005743-02
Application #
2430005
Study Section
Special Emphasis Panel (SRCD (11))
Project Start
1997-06-15
Project End
Budget Start
1997-06-15
Budget End
1998-05-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Tulane University
Department
Type
Other Domestic Higher Education
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118