The demonstration of a change in responsiveness of mice to physostigmine and atropine after withdrawal from long-term haloperidol pretreatment.
Mice, administered haloperidol 3 mg/kg/day, in their drinking water for 21 days, were tested for their responsiveness to cholinergic and anticholinergic drugs 4 days after withdrawal from haloperidol (or vehicle). Haloperidol-treated animals administered methylhyoscine (1 mg/kg i.p.) and various doses of physostigmine (5 to 1215 microgram/kg) displayed significantly less depression of locomotor activity than vehicle-treated animals. Atropine, 5 mg/kg, whilst ineffective in producing locomotor stimulation in vehicle-treated animals, produced marked stimulation in haloperidol-treated animals. Methylatropine (5 mg/kg) did not produce significant stimulation in either group. Dopamine receptor supersensitivity was present in these animals as haloperidol-treated mice, pretreated with alpha-methyltyrosine and reserpine, displayed a significantly greater locomotor response to apomorphine than did vehicle-treated animals. The data support the hypothesis that long-term administration of haloperidol produces an apparent hyposensitivity of central muscarinic receptors.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010830:Physostigmine / Q000494:pharmacology*; D011292:Premedication; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects
D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D001285:Atropine; D010830:Physostigmine; D006220:Haloperidol; D001058:Apomorphine