@article{a0fbcf90430c11df928f000ea68e967b,
title = "A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors",
abstract = "Acetylcholine (ACh) regulates many key functions of the CNS by activating cell surface receptors referred to as muscarinic ACh receptors (M 1-M5 mAChRs). Like other mAChR subtypes, the M4 mAChRis widely expressed in different regions of the forebrain. Interestingly,M4 mAChRs are coexpressed with D1 dopamine receptors in a specific subset of striatal projection neurons. To investigate the physiological relevance of this M4 mAChR subpopulation in modulating dopamine-dependent behaviors, we used Cre/loxP technology to generate mutant mice that lack M4 mAChRs only in D1 dopamine receptor-expressing cells. The newly generated mutant mice displayed several striking behavioral phenotypes, including enhanced hyperlocomotor activity and increased behavioral sensitization following treatment with psychostimulants. These behavioral changes were accompanied by a lack of muscarinic inhibition of D1 dopamine receptor-mediated cAMP stimulation in the striatum and an increase in dopamine efflux in the nucleus accumbens. These novel findings demonstrate that a distinct subpopulation of neuronal M4 mAChRs plays a critical role in modulating several important dopamine-dependent behaviors. Since enhanced central dopaminergic neurotransmission is a hallmark of several severe disorders of the CNS, including schizophrenia and drug addiction, our findings have substantial clinical relevance.",
author = "Jongrye Jeon and Ditte Dencker and Gitta W{\"o}rtwein and Woldbye, {David P D} and Yinghong Cui and Davis, {Albert A} and Levey, {Allan I} and G{\"u}nther Sch{\"u}tz and Sager, {Thomas N} and Arne M{\o}rk and Cuiling Li and Chu-Xia Deng and Anders Fink-Jensen and J{\"u}rgen Wess and Jongrye Jeon and Nielsen, {Ditte Dencker} and Gitta W{\"o}rtwein and Woldbye, {David P D} and Yinghong Cui and Davis, {Albert A} and Levey, {Allan I} and G{\"u}nther Sch{\"u}tz and Sager, {Thomas N} and Arne M{\o}rk and Cuiling Li and Chu-Xia Deng and Anders Fink-Jensen and J{\"u}rgen Wess",
note = "Keywords: Amphetamine; Animals; Antipsychotic Agents; Behavior, Animal; Central Nervous System Stimulants; Cocaine; Corpus Striatum; Cyclic AMP; Dopamine; Mice; Mice, Mutant Strains; Motor Activity; Neurons; Nucleus Accumbens; Receptor, Muscarinic M4; Receptors, Dopamine D1",
year = "2010",
month = feb,
day = "10",
doi = "10.1523/JNEUROSCI.3843-09.2010",
language = "English",
volume = "30",
pages = "2396--405",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "6",
}
