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The 5‐HT 3 Antagonist MDL‐72222 Exacerbates Ethanol Withdrawal Seizures in Mice
Author(s) -
Grant Kathleen A.,
Hellevuo Kaisa,
Tabakoff Boris
Publication year - 1994
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1994.tb00034.x
Subject(s) - antagonist , ethanol , pharmacology , psychology , zoology , medicine , biology , receptor , biochemistry
Ethanol‐dependent mice were treated with the 5‐HT 3 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‐HT 3 antagonist, ICS 205‐930 (23 and 46 mg/kg), or the 5‐ HT 2 receptor antagonist ketanserin, did not affect ethanol withdrawal seizures. The findings suggest MDL 72222 selectively enhances sensitivity to withdrawal seizures following chronic ethanol exposure.