DOI: 10.1073/pnas.96.18.10483. Enhancement of D1 dopamine receptor-mediated locomotor stimulation in M <sub>4</sub> muscarinic acetylcholine receptor knockout mice

Enhancement of D1 dopamine receptor-mediated locomotor stimulation in M 4 muscarinic acetylcholine receptor knockout mice

10.1073/pnas.96.18.10483

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Muscarinic acetylcholine receptors (M 1 –M 5 ) regulate many key functions of the central and peripheral nervous system. Primarily because of the lack of receptor subtype-selective ligands, the precise physiological roles of the individual muscarinic receptor subtypes remain to be elucidated. Interestingly, the M 4 receptor subtype is expressed abundantly in the striatum and various other forebrain regions. To study its potential role in the regulation of locomotor activity and other central functions, we used gene-targeting technology to create mice that lack functional M 4 receptors. Pharmacologic analysis of M 4 receptor-deficient mice indicated that M 4 receptors are not required for muscarinic receptor-mediated analgesia, tremor, hypothermia, and salivation. Strikingly, M 4 receptor-deficient mice showed an increase in basal locomotor activity and greatly enhanced locomotor responses (as compared with their wild-type littermates) after activation of D1 dopamine receptors. These results indicate that M 4 receptors exert inhibitory control on D1 receptor-mediated locomotor stimulation, probably at the level of striatal projection neurons where the two receptors are coexpressed at high levels. Our findings offer new perspectives for the treatment of Parkinson’s disease and other movement disorders that are characterized by an imbalance between muscarinic cholinergic and dopaminergic neurotransmission.

Bibliography

Gomeza, J., Zhang, L., Kostenis, E., Felder, C., Bymaster, F., Brodkin, J., Shannon, H., Xia, B., Deng, C., & Wess, J. (1999). Enhancement of D1 dopamine receptor-mediated locomotor stimulation in M 4 muscarinic acetylcholine receptor knockout mice. Proceedings of the National Academy of Sciences, 96(18), 10483â10488.

Authors 10

Jesus Gomeza (first)
Lu Zhang (additional)
Evi Kostenis (additional)
Christian Felder (additional)
Frank Bymaster (additional)
Jesse Brodkin (additional)
Harlan Shannon (additional)
Bing Xia (additional)
Chu-xia Deng (additional)
Jürgen Wess (additional)

References 41 Referenced 261

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:31 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 4:23 p.m.)
Indexed	1 month ago (Aug. 5, 2025, 8:50 a.m.)
Issued	26 years ago (Aug. 31, 1999)
Published	26 years ago (Aug. 31, 1999)
Published Online	26 years ago (Aug. 31, 1999)
Published Print	26 years ago (Aug. 31, 1999)

Funders 0

None

BibTeX

@article{Gomeza_1999, title={Enhancement of D1 dopamine receptor-mediated locomotor stimulation in M 4 muscarinic acetylcholine receptor knockout mice}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.18.10483}, DOI={10.1073/pnas.96.18.10483}, number={18}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Gomeza, Jesus and Zhang, Lu and Kostenis, Evi and Felder, Christian and Bymaster, Frank and Brodkin, Jesse and Shannon, Harlan and Xia, Bing and Deng, Chu-xia and Wess, Jürgen}, year={1999}, month=aug, pages={10483–10488} }

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      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}