Central muscarinic cholinergic influences on ethanol sensitivity in long-sleep and short-sleep mice

V. G. Erwin, A. Korte, Byron Jones

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Sensitivity to the hypnotic effects of ethanol was increased selectively by central administration of muscarinic agonists. Carbachol or oxotremorine, but not nicotine, i.c.v., enhanced hypnotic sensitivity to ethanol markedly, as measured by blood ethanol concentration at loss or righting response, in short-sleep (SS) but not long-sleep (LS) mice. Likewise, the acetylcholinesterase inhibitor, neostigmine, i.c.v., differentially enhanced hypnotic sensitivity to ethanol in these mouse lines.LS and SS mice were equally sensitive to the hypothermic effects of carbachol, neostigmine or oxotremorine i.c.v. The muscarinic antagonists, atropine or pirenzepine, i.c.v., were without effect on ethanol sensitivity, but these compounds antagonized muscarinic agonist-enhanced ethanol sensitivity in SS mice effectively. Pirenzepine, and M1 selective antagonist, produced a parallel shift in the oxotremorine dose-response curve, indicating that the enhanced hypnotic sensitivity to ethanol may be due to interaction of oxotremorine with M1 muscarinic receptors. This possibility was supported by the finding that atropine and pirenzepine which are known to have comparable affinities for M1 but not M2 receptors, had comparable potencies in antagonizing the action of oxotremorine or neostigmine. The results suggest that LS and SS mice differ genetically in neuronal processes activated by specific muscarinic agonists and are consistent with the hypotheses that ethanol acts in part via membrane receptor coupling to intracellular processes known to mobilize intracellular Ca++.

Original languageEnglish (US)
Pages (from-to)857-862
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume247
Issue number3
StatePublished - Dec 1 1988

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Cholinergic Agents
Oxotremorine
Sleep
Ethanol
Hypnotics and Sedatives
Pirenzepine
Neostigmine
Muscarinic Agonists
Carbachol
Atropine
Muscarinic M1 Receptors
Righting Reflex
Muscarinic Antagonists
Cholinesterase Inhibitors
Nicotine
Membranes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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Central muscarinic cholinergic influences on ethanol sensitivity in long-sleep and short-sleep mice. / Erwin, V. G.; Korte, A.; Jones, Byron.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 247, No. 3, 01.12.1988, p. 857-862.

Research output: Contribution to journalArticle

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