Shannon_1990_J.Pharmacol.Exp.Ther_255_549

The effects of cholinesterase inhibitors, cholinergic agonists, dopaminergic agonists and dopaminergic antagonists on the hyperactivity produced by the muscarinic cholinergic antagonist scopolamine were evaluated in mice. Scopolamine (0.3-10 mg/kg) produced a dose-related increase in locomotor activity, with a peak effect at 3.0 mg/kg. The cholinesterase inhibitor physostigmine (0.03-0.175 mg/kg) was without effect on locomotor activity when administered alone, whereas the cholinesterase inhibitor tetrahydroaminoacridine hydrate (0.3-10 mg/kg) decreased locomotor activity. Both physostigmine and tetrahydroaminoacridine hydrate attenuated the effects of scopolamine. Administered alone, the cholinergic agonists oxotremorine (0.01-0.3 mg/kg) and RS86 (0.1-3.0 mg/kg) produced dose-related decreases in locomotor activity, whereas pilocarpine (0.3-10 mg/kg) had no effect on locomotor activity. None of these three muscarinic agonists significantly attenuated the hyperactivity produced by scopolamine. Administered alone, the dopaminergic agonists quinpirole (0.003-0.1 mg/kg), S-(-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine (0.3-10 mg/kg) and SKF 38393 (8-64 mg/kg) had no significant effect on activity, whereas apomorphine (0.3-10 mg/kg) and d-amphetamine (0.1-3.0 mg/kg) increased activity. Quinpirole, apomorphine and S-(-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine produced dose-related reversals of the increases in locomotor activity produced by scopolamine. The hyperactivity effects of d-amphetamine were approximately additive with scopolamine, whereas SKF 38393 did not significantly affect scopolamine. The mixed D1/D2 dopaminergic antagonist haloperidol (0.003-3.0 mg/kg) and the selective D1 antagonist SCH 23390 (0.01-0.3 mg/kg) produced dose-related decreases in locomotor activity when administered alone, and also produced dose-related reversals of the hyperactivity produced by scopolamine.(ABSTRACT TRUNCATED AT 250 WORDS)