ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Involvement of a subpopulation of neuronal M4 muscarinic acetylcholine receptors in the antipsychotic-like effects of the M1/M4 preferring muscarinic receptor agonist xanomeline.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 62 citations in OpenAlex.
- Pharmacological reduction of reverse-translated hippocampal hyperactivity in mouse: relevance for psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- From theory to therapy: unlocking the potential of muscarinic receptor activation in schizophrenia with the dual M1/M4 muscarinic receptor agonist xanomeline and trospium chloride and insights from clinical trials.The international journal of neuropsychopharmacology · 2025Review
- Visual hallucinations in Parkinson's disease: spotlight on central cholinergic dysfunction.Brain : a journal of neurology · 2025Review
- Current Findings and Potential Mechanisms of KarXT (Xanomeline-Trospium) in Schizophrenia Treatment.Clinical drug investigation · 2024Review
- Normative modelling of molecular-based functional circuits captures clinical heterogeneity transdiagnostically in psychiatric patients.Communications biology · 2024Article
- Targeting the Actions of Muscarinic Receptors on Dopamine Systems: New Strategies for Treating Neuropsychiatric Disorders.Annual review of pharmacology and toxicology · 2024Review
- Potential of olfactory neuroepithelial cells as a model to study schizophrenia: A focus on GPCRs (Review).International journal of molecular medicine · 2024Review
- Article
- Progress in mechanistically novel treatments for schizophrenia.RSC medicinal chemistry · 2021Review
- Targeting muscarinic receptors to treat schizophrenia.Behavioural brain research · 2021Review
- Dangerous Liaisons: Tau Interaction with Muscarinic Receptors.Current Alzheimer research · 2020Review
- Targeting Muscarinic Acetylcholine Receptors for the Treatment of Psychiatric and Neurological Disorders.Trends in pharmacological sciences · 2019Review
- Roles of the MMovement disorders : official journal of the Movement Disorder Society · 2019Review
- Positive allosteric modulation of MNeuropharmacology · 2018Review
- Physiological roles of CNS muscarinic receptors gained from knockout mice.Neuropharmacology · 2018Review
- Vertical exploration and dimensional modularity in mice.Royal Society open science · 2018Article
- Muscarinic receptor MDrug and alcohol dependence · 2017Article
- Prediction of consensus binding mode geometries for related chemical series of positive allosteric modulators of adenosine and muscarinic acetylcholine receptors.Journal of computational chemistry · 2017Article
- Review
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Disturbances in central dopaminergic neurotransmission are believed to be centrally involved in the pathogenesis of schizophrenia. Central dopaminergic and cholinergic systems interact and the cholinergic muscarinic agonist xanomeline has shown antipsychotic effects in clinical studies. Preclinical studies indicate that the M(4) muscarinic cholinergic receptor subtype (mAChR) modulates the activity of the dopaminergic system and that this specific mAChR subtype is involved in mediating the antipsychotic-like effects of xanomeline. A specific neuronal subpopulation that expresses M(4) mAChRs together with D(1) dopamine receptors seems to be especially important in modulating dopamine-dependent behaviors. Using mutant mice that lack the M(4) mAChR only in D(1) dopamine receptor-expressing cells (D1-M4-KO), we investigated the role of this neuronal population in the antipsychotic-like effects of xanomeline in amphetamine-induced hyperactivity and apomorphine-induced climbing. Interestingly, the antipsychotic-like effects of xanomeline in the two models were almost completely abolished in D1-M4-KO mice, suggesting that M(4) mAChRs colocalized with D(1) dopamine receptors are centrally involved in mediating the antipsychotic-like effects of xanomeline. This is consistent with the hypothesis that activation of the M(4) mAChR represents a potential target for the future medical treatment of psychosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.