The protein product of CHRM3 is the muscarinic AChR M3, which is localized to multiple tissues, including the brain, smooth muscle, endocrine and exocrine glands, and lungs. In human, mutation of CHRM3 causes disease of the urinary bladder and a prune-belly-like syndrome22. In mice, cannabinoids consistently increase acetylcholine (ACh) and decrease ACh turnover in the HIPP23. Pharmacological evidence has also implicated cholinergic dysfunction in the manifestation of psychotic symptoms. Muscarinic ACh receptors (AChRs) play important roles in animal models that are used to examine sensory gating, which is known to be disrupted in schizophrenic patients, and the activation of muscarinic AChRs was suggested as an alternative to classical antipsychotics for the treating of psychotic symptoms23. Chrm3 knockout mice treated with the antipsychotic drug oxotremorine that acts as a selective muscarinic ACh receptor agonist24–26 displayed increased dopamine release, which is consistent with Chrm3 playing an inhibitory role in dopamine release24. In animal models, oxotremorine can reverse methamphetamine-, ketamine-, and cocaine-induced hyperlocomotion26. Blockade of cholinergic receptors, particularly muscarinic receptors, causes a psychosis characterized by hallucinations and cognitive impairment in normal human subjects
