The M5 muscarinic receptor as possible target for treatment of drug abuse

Two reports published in the latter 1980s are generally given credit for being the first to announce the discovery of a new subtype of muscarinic acetylcholine receptor (mAChR), designated m5 or M5, and now officially M(5) (1). Both identifications were assigned using molecular biology techniques. Then - as now - no selective high-affinity ligands or toxins were available. In situ hybridization and reverse-transcriptase PCR have found M(5) AChR expression in brain to be distinct from that of the four other G protein-coupled mAChR subtypes and primarily localized to the substantia nigra, ventral tegmental area, hippocampus (CA1 and CA2 subfields), cerebral cortex (outermost layer) and striatum (caudate putamen). M(5) AChR brain region localization and involvement in the regulation of striatal dopamine release and in rewarding brain stimulation suggests a possible role for M(5) AChR as a target for novel therapy to treat excess hedonic drive, including drug abuse.