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.