p(MGI:Chrm4)
Corroborating this hypothesis, it has been demonstrated that dopamine efflux is increased in the nucleus accumbens of M4 knockout mice PubMed:26813123
M4 mAChR is mainly expressed in the corpus striatum in the CNS and on various prejunctional nerve terminals in the periphery. M4 mAChR has been suggested to play a role in psychosis and to be a promising target for the treatment of schizophrenia[52]. Indeed, the mixed M1/M4 mAChR agonist xanomeline has antipsychotic effects, and M4 mAChR-knockout mice display increased sensitivity to the disruptive effects of phencyclidine, a drug of abuse PubMed:24590577
M4 mAChR is also involved in the pathology of Parkinson’s disease, which is associated with the loss of dopaminergic neurons projecting to the striatum and an imbalance between cholinergic and dopaminergic systems. In the corpus striatum, M4 mAChR is closely co-localized with dopamine receptors on striatal-projecting neurons and the striatal M4 mAChR inhibits dopamine D1 receptor function. Mice lacking M4 mAChR show increased locomotor activity and enhanced dopamine D1 receptor-mediated effects[55]. Consequently, selective M4 mAChR antagonists, such as benzoxazines, have been developed for the treatment of Parkinson’s disease PubMed:24590577
M4 mAChR is also involved in the pathology of Parkinson’s disease, which is associated with the loss of dopaminergic neurons projecting to the striatum and an imbalance between cholinergic and dopaminergic systems. In the corpus striatum, M4 mAChR is closely co-localized with dopamine receptors on striatal-projecting neurons and the striatal M4 mAChR inhibits dopamine D1 receptor function. Mice lacking M4 mAChR show increased locomotor activity and enhanced dopamine D1 receptor-mediated effects[55]. Consequently, selective M4 mAChR antagonists, such as benzoxazines, have been developed for the treatment of Parkinson’s disease PubMed:24590577
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.