Attenuation of amphetamine-induced activity by the non-selective muscarinic receptor agonist, xanomeline, is absent in muscarinic M 4 receptor knockout mice and attenuated in muscarinic M 1 receptor knockout mice

Abstract

The muscarinic acetylcholine receptor (mAChR) agonist, xanomeline, attenuates amphetamine-induced activity in WT mice. This effect is abolished in mice lacking the M 4 muscarinic acetylcholine receptor (M 4 mAChR KO) and partially attenuated in mice lacking M 1 muscarinic acetylcholine receptor (M 1 mAChR KO). Collectively, these data suggest that the efficacy exhibited by xanomeline in the mouse amphetamine-induced hyperactivity model, is mediated predominantly by M 4 muscarinic acetylcholine receptors, and that M 1 muscarinic acetylcholine receptors may play a more minor role. This supports the hypothesis that activation of M 4, and to a lesser extent M 1 muscarinic acetylcholine receptors, may represent a potential target for the treatment of psychosis seen in schizophrenia.