The 5-HT3 antagonist MDL-72222 exacerbates ethanol withdrawal seizures in mice

Kathleen (Kathy) Grant, K. Hellevuo, B. Tabakoff

Research output: Contribution to journalArticle

24 Citations (Scopus)

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
StatePublished - 1994
Externally publishedYes

Fingerprint

Serotonin 5-HT3 Receptor Antagonists
Seizures
Ethanol
tropisetron
Serotonin 5-HT2 Receptor Antagonists
Ketanserin
bemesetron

Keywords

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

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

The 5-HT3 antagonist MDL-72222 exacerbates ethanol withdrawal seizures in mice. / Grant, Kathleen (Kathy); Hellevuo, K.; Tabakoff, B.

In: Alcoholism: Clinical and Experimental Research, Vol. 18, No. 2, 1994, p. 410-414.

Research output: Contribution to journalArticle

@article{a8d71a0723864a75976337a473507ccc,
title = "The 5-HT3 antagonist MDL-72222 exacerbates ethanol withdrawal seizures in mice",
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.",
keywords = "5-HT Antagonists, Alcohol Dependence, Drug Withdrawal Seizures, Serotonin",
author = "Grant, {Kathleen (Kathy)} and K. Hellevuo and B. Tabakoff",
year = "1994",
language = "English (US)",
volume = "18",
pages = "410--414",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - The 5-HT3 antagonist MDL-72222 exacerbates ethanol withdrawal seizures in mice

AU - Grant, Kathleen (Kathy)

AU - Hellevuo, K.

AU - Tabakoff, B.

PY - 1994

Y1 - 1994

N2 - 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.

AB - 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.

KW - 5-HT Antagonists

KW - Alcohol Dependence

KW - Drug Withdrawal Seizures

KW - Serotonin

UR - http://www.scopus.com/inward/record.url?scp=0028177044&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028177044&partnerID=8YFLogxK

M3 - Article

C2 - 8048747

AN - SCOPUS:0028177044

VL - 18

SP - 410

EP - 414

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 2

ER -