Muscarinic antagonists attenuate dizocilpine-induced hypermotility in mice.
Pretreatment of mice with the muscarinic receptor antagonists scopolamine and atropine attenuated the hypermotility (but not the depression of rearing) induced by a low dose of dizocilpine maleate [(+)-MK-801; 0.1 mg/kg, i.p.], a non-competitive NMDA antagonist. In contrast, the muscarinic blockers failed to affect hypermotility induced by equieffective doses of phencyclidine (1 mg/kg, i.p.) or d-amphetamine (2 mg/kg, i.p.). These results suggest differences between the mechanism of behavioral activation produced by dizocilpine and phencyclidine, and demonstrate the potential of muscarinic blockade for diminishing the behavioral toxicity of NMDA antagonists.
Lapin
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Neuronal Excitability Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Rogawski
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MA
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology
D010276:Parasympatholytics; D016291:Dizocilpine Maleate; D001285:Atropine; D012601:Scopolamine; D010622:Phencyclidine; D003913:Dextroamphetamine