The 5‐HT3 Antagonist MDL‐72222 Exacerbates Ethanol Withdrawal Seizures in Mice

Kathleen A. Grant, Kaisa Hellevuo, Boris Tabakoff

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Ethanol‐dependent mice were treated with the 5‐HT3 antagonist MDL 72222 after withdrawal from ethanol. Treatment with unit doses (0, 5.6, 10, and 17.0 mg/kg) of MDL 72222 at 0, 4, and 7 hr after withdrawal dose‐dependently exacerbated the severity of ethanol withdrawal seizures. Treatment with a single dose (17 mg/kg) of MDL 72222 at 5 hr after withdrawal also exacerbated the severity of ethanol withdrawal seizures. Ethanol naive mice treated with MDL 72222 (56 mg/kg) did not display any seizures. Treatment with another 5‐HT3 antagonist, ICS 205‐930 (23 and 46 mg/kg), or the 5‐ HT2 receptor antagonist ketanserin, did not affect ethanol withdrawal seizures. The findings suggest MDL 72222 selectively enhances sensitivity to withdrawal seizures following chronic ethanol exposure.

Original languageEnglish (US)
Pages (from-to)410-414
Number of pages5
JournalAlcoholism: Clinical and Experimental Research
Volume18
Issue number2
DOIs
StatePublished - Apr 1994
Externally publishedYes

Keywords

  • 5‐HT Antagonists
  • Alcohol Dependence
  • Drug Withdrawal Seizures
  • Serotonin

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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