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Volume 7, Pages 64-73
Mini-Review Article

An Emerging Role for the Delta Opioid Receptor in the Regulation of Mu Opioid Receptor Function

Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA

Received 25 June 2007; Revised 26 July 2007; Accepted 30 July 2007

Academic Editors: D. Shurtleff and S. Ferre

Copyright © 2007 Raphael Rozenfeld et al.


Morphine and related opiates are commonly used in the clinical management of various types of pain. However, the antinociceptive properties of morphine are often overshadowed by the development of tolerance and dependence following its chronic use. The mechanisms underlying opiate tolerance are not fully understood, but appear to involve numerous and complex physiological adaptations. Recently, a role for the heterodimerization of mu and delta opioid receptors in the development of morphine tolerance has been proposed. This novel mechanism could help us to understand several observations, such as the critical role of delta opioid receptor regulation, the impact of delta opioid receptor binding site occupancy, and the participation of beta-arrestin2, in the development of morphine tolerance.