Attenuation of amphetamine-induced activity by the non-selective muscarinic receptor agonist, xanomeline, is absent in muscarinic M4 receptor knockout mice and attenuated in muscarinic M1 receptor knockout mice

The muscarinic acetylcholine receptor (mAChR) agonist, xanomeline, attenuates amphetamine-induced activity in WT mice. This effect is abolished in mice lacking the M(4) muscarinic acetylcholine receptor (M(4) mAChR KO) and partially attenuated in mice lacking M(1) muscarinic acetylcholine receptor (...

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Bibliographic Details
Published in:European journal of pharmacology 2009-01, Vol.603 (1-3), p.147-149
Main Authors: WOOLLEY, Marie L, CARTER, Helen J, GARTLON, Jane E, WATSON, Jeanette M, DAWSON, Lee A
Format: Article
Language:English
Subjects:
Adult and adolescent clinical studies
Amphetamine - toxicity
Animals
Biological and medical sciences
Hyperkinesis - chemically induced
Hyperkinesis - drug therapy
Medical sciences
Mice
Mice, Knockout
Muscarinic Agonists - pharmacology
Muscarinic Agonists - therapeutic use
Pharmacology. Drug treatments
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Psychoses
Pyridines - pharmacology
Pyridines - therapeutic use
Receptor, Muscarinic M1 - deficiency
Receptor, Muscarinic M1 - genetics
Receptor, Muscarinic M4 - deficiency
Receptor, Muscarinic M4 - genetics
Schizophrenia
Substrate Specificity
Thiadiazoles - pharmacology
Thiadiazoles - therapeutic use
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Summary:The muscarinic acetylcholine receptor (mAChR) agonist, xanomeline, attenuates amphetamine-induced activity in WT mice. This effect is abolished in mice lacking the M(4) muscarinic acetylcholine receptor (M(4) mAChR KO) and partially attenuated in mice lacking M(1) muscarinic acetylcholine receptor (M(1) mAChR KO). Collectively, these data suggest that the efficacy exhibited by xanomeline in the mouse amphetamine-induced hyperactivity model, is mediated predominantly by M(4) muscarinic acetylcholine receptors, and that M(1) muscarinic acetylcholine receptors may play a more minor role. This supports the hypothesis that activation of M(4), and to a lesser extent M(1) muscarinic acetylcholine receptors, may represent a potential target for the treatment of psychosis seen in schizophrenia.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2008.12.020