Involvement of a subpopulation of neuronal M4 muscarinic acetylcholine receptors in the antipsychotic-like effects of the M1/M4 preferring muscarinic receptor agonist xanomeline

Research output: Contribution to journalJournal articlepeer-review

Standard

Involvement of a subpopulation of neuronal M4 muscarinic acetylcholine receptors in the antipsychotic-like effects of the M1/M4 preferring muscarinic receptor agonist xanomeline. / Dencker, Ditte; Wörtwein, Gitta; Weikop, Pia; Jeon, Jongrye; Thomsen, Morgane; Sager, Thomas N.; Mørk, Arne; Woldbye, David Paul Drucker; Wess, Jürgen; Fink-Jensen, Anders.

In: Journal of Neuroscience, Vol. 31, No. 16, 2011, p. 5905-8.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Dencker, D, Wörtwein, G, Weikop, P, Jeon, J, Thomsen, M, Sager, TN, Mørk, A, Woldbye, DPD, Wess, J & Fink-Jensen, A 2011, 'Involvement of a subpopulation of neuronal M4 muscarinic acetylcholine receptors in the antipsychotic-like effects of the M1/M4 preferring muscarinic receptor agonist xanomeline', Journal of Neuroscience, vol. 31, no. 16, pp. 5905-8. https://doi.org/10.1523/JNEUROSCI.0370-11.2011

APA

Dencker, D., Wörtwein, G., Weikop, P., Jeon, J., Thomsen, M., Sager, T. N., Mørk, A., Woldbye, D. P. D., Wess, J., & Fink-Jensen, A. (2011). Involvement of a subpopulation of neuronal M4 muscarinic acetylcholine receptors in the antipsychotic-like effects of the M1/M4 preferring muscarinic receptor agonist xanomeline. Journal of Neuroscience, 31(16), 5905-8. https://doi.org/10.1523/JNEUROSCI.0370-11.2011

Vancouver

Dencker D, Wörtwein G, Weikop P, Jeon J, Thomsen M, Sager TN et al. Involvement of a subpopulation of neuronal M4 muscarinic acetylcholine receptors in the antipsychotic-like effects of the M1/M4 preferring muscarinic receptor agonist xanomeline. Journal of Neuroscience. 2011;31(16):5905-8. https://doi.org/10.1523/JNEUROSCI.0370-11.2011

Author

Dencker, Ditte ; Wörtwein, Gitta ; Weikop, Pia ; Jeon, Jongrye ; Thomsen, Morgane ; Sager, Thomas N. ; Mørk, Arne ; Woldbye, David Paul Drucker ; Wess, Jürgen ; Fink-Jensen, Anders. / Involvement of a subpopulation of neuronal M4 muscarinic acetylcholine receptors in the antipsychotic-like effects of the M1/M4 preferring muscarinic receptor agonist xanomeline. In: Journal of Neuroscience. 2011 ; Vol. 31, No. 16. pp. 5905-8.

Bibtex

@article{8fe62b674f93480fa2d347528baad110,
title = "Involvement of a subpopulation of neuronal M4 muscarinic acetylcholine receptors in the antipsychotic-like effects of the M1/M4 preferring muscarinic receptor agonist xanomeline",
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.",
keywords = "Amphetamine, Analysis of Variance, Animals, Behavior, Animal, Central Nervous System Stimulants, Hyperkinesis, Mice, Mice, Knockout, Motor Activity, Muscarinic Agonists, Neurons, Pyridines, Receptor, Muscarinic M4, Thiadiazoles",
author = "Ditte Dencker and Gitta W{\"o}rtwein and Pia Weikop and Jongrye Jeon and Morgane Thomsen and Sager, {Thomas N.} and Arne M{\o}rk and Woldbye, {David Paul Drucker} and J{\"u}rgen Wess and Anders Fink-Jensen",
year = "2011",
doi = "10.1523/JNEUROSCI.0370-11.2011",
language = "English",
volume = "31",
pages = "5905--8",
journal = "The Journal of neuroscience : the official journal of the Society for Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "16",

}

RIS

TY - JOUR

T1 - Involvement of a subpopulation of neuronal M4 muscarinic acetylcholine receptors in the antipsychotic-like effects of the M1/M4 preferring muscarinic receptor agonist xanomeline

AU - Dencker, Ditte

AU - Wörtwein, Gitta

AU - Weikop, Pia

AU - Jeon, Jongrye

AU - Thomsen, Morgane

AU - Sager, Thomas N.

AU - Mørk, Arne

AU - Woldbye, David Paul Drucker

AU - Wess, Jürgen

AU - Fink-Jensen, Anders

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - Amphetamine

KW - Analysis of Variance

KW - Animals

KW - Behavior, Animal

KW - Central Nervous System Stimulants

KW - Hyperkinesis

KW - Mice

KW - Mice, Knockout

KW - Motor Activity

KW - Muscarinic Agonists

KW - Neurons

KW - Pyridines

KW - Receptor, Muscarinic M4

KW - Thiadiazoles

U2 - 10.1523/JNEUROSCI.0370-11.2011

DO - 10.1523/JNEUROSCI.0370-11.2011

M3 - Journal article

C2 - 21508215

VL - 31

SP - 5905

EP - 5908

JO - The Journal of neuroscience : the official journal of the Society for Neuroscience

JF - The Journal of neuroscience : the official journal of the Society for Neuroscience

SN - 0270-6474

IS - 16

ER -

ID: 33916938