Muscarinic receptors: a novel therapeutic target for drug addiction

Abstract

A recent study has provided direct evidence supporting a role for muscarinic acetylcholine receptors in the rewarding effects of opiates. Using gene-targeting approaches to generate mice deficient in muscarinic M5 receptors, Basile and colleagues [ 1. Basile A.S. et al. Deletion of the M5 muscarinic acetylcholine receptor attenuates morphine reinforcement and withdrawal but not morphine analgesia. Proc. Natl. Acad. Sci. U. S. A. 2002; 99: 11452-11457 Crossref PubMed Scopus (153) Google Scholar ] showed that the rewarding effects of morphine, as measured in the conditioned place-preference paradigm, were greatly reduced in these mice. However, the analgesic efficacy of morphine and the development of tolerance to the analgesic effects of morphine remained unaltered in these M5-receptor-deficient mice. Thus, the authors suggest that M5 receptors might represent a novel target for the treatment of opiate addiction.