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The demonstration of a change in responsiveness of mice to physostigmine and atropine after withdrawal from long-term haloperidol pretreatment.

Authors
  • Dunstan, R
  • Jackson, D M
Type
Published Article
Journal
Journal of neural transmission
Publication Date
Jan 01, 1977
Volume
40
Issue
3
Pages
181–189
Identifiers
PMID: 874470
Source
Medline
License
Unknown

Abstract

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.

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