Role for M5 muscarinic acetylcholine receptors in cocaine addiction

✍ Scribed by Anders Fink-Jensen; Irina Fedorova; Gitta Wörtwein; David P. D. Woldbye; Thøger Rasmussen; Morgane Thomsen; Tom G. Bolwig; Karen M. Knitowski; David L. McKinzie; Masahisa Yamada; Jürgen Wess; Anthony Basile

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 90 KB
• Volume: 74
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.10728

✦ Synopsis

Muscarinic cholinergic receptors of the M 5 subtype are expressed by dopamine-containing neurons of the ventral tegmentum. These M 5 receptors modulate the activity of midbrain dopaminergic neurons, which play an important role in mediating reinforcing properties of abused psychostimulants like cocaine. The potential role of M 5 receptors in the reinforcing effects of cocaine was investigated using M 5 receptor-deficient mice in a model of acute cocaine self-administration. The M 5 -deficient mice self-administered cocaine at a significantly lower rate than wild-type controls. In the conditioned place preference procedure, a classic test for evaluating the rewarding properties of drugs, M 5 -deficient mice spent significantly less time in the cocaine-paired compartment than control mice. Moreover, the severity of the cocaine withdrawal syndrome (withdrawal-associated anxiety measured in the elevated plus-maze) was significantly attenuated in mice lacking the M 5 receptor. These results demonstrate that M 5 receptors play an important role in mediating both cocaine-associated reinforcement and withdrawal.