The 5-HT3 antagonist MDL-72222 exacerbates ethanol withdrawal seizures in mice.
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.
Grant
K A
KA
Division of Clinical and Biologic Research, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD.
Hellevuo
K
K
Tabakoff
B
B
D000430:Alcohol Withdrawal Delirium / Q000503:physiopathology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D004856:Postural Balance / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D012640:Seizures / Q000503:physiopathology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014326:Tropanes / Q000494:pharmacology*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; D007650:Ketanserin; C042253:bemesetron