PT  - JOURNAL ARTICLE
AU  - Ditte Dencker
AU  - Gitta Wörtwein
AU  - Pia Weikop
AU  - Jongrye Jeon
AU  - Morgane Thomsen
AU  - Thomas N. Sager
AU  - Arne Mørk
AU  - David P. D. Woldbye
AU  - Jürgen Wess
AU  - Anders Fink-Jensen
TI  - Involvement of a Subpopulation of Neuronal M&lt;sub&gt;4&lt;/sub&gt; Muscarinic Acetylcholine Receptors in the Antipsychotic-like Effects of the M&lt;sub&gt;1&lt;/sub&gt;/M&lt;sub&gt;4&lt;/sub&gt; Preferring Muscarinic Receptor Agonist Xanomeline
AID  - 10.1523/JNEUROSCI.0370-11.2011
DP  - 2011 Apr 20
TA  - The Journal of Neuroscience
PG  - 5905--5908
VI  - 31
IP  - 16
4099  - http://www.jneurosci.org/content/31/16/5905.short
4100  - http://www.jneurosci.org/content/31/16/5905.full
SO  - J. Neurosci.2011 Apr 20; 31
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 M4 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 M4 mAChRs together with D1 dopamine receptors seems to be especially important in modulating dopamine-dependent behaviors. Using mutant mice that lack the M4 mAChR only in D1 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 M4 mAChRs colocalized with D1 dopamine receptors are centrally involved in mediating the antipsychotic-like effects of xanomeline. This is consistent with the hypothesis that activation of the M4 mAChR represents a potential target for the future medical treatment of psychosis.