Ethanol blocks nicotine-induced seizures in mice: comparison with midazolam and baclofen.
Low doses of ethanol may antagonize the pharmacological effects of nicotine. Recently, it has been shown that the effects of ethanol on nicotine discrimination are not correlated with blood ethanol levels. The aim of the present study was to evaluate whether ethanol (0.5-2g/kg, i.p.) could block nicotine-induced seizures in C57BL/6J mice and to correlate ethanol's actions with blood ethanol concentrations. For comparison, the effects of a gamma-aminobutyric acid A (GABAA)/benzodiazepine receptor positive modulator, midazolam (0.25-40 mg/kg, i.p.), and a gamma-aminobutyric acid B receptor agonist, baclofen (2.5-20 mg/kg, i.p.), were assessed in the same procedure. Nicotine (3-9 mg/kg, s.c.) induced clonic-tonic seizures in a dose-dependent manner. Ethanol, administered 5 or 50 min before nicotine, dose dependently antagonized seizures elicited by 6 mg/kg nicotine. The anticonvulsant effects of ethanol correlated with blood ethanol levels and were comparable to those exerted by midazolam. Baclofen antagonized only the tonic component of nicotine-induced convulsions. The anticonvulsant doses of ethanol (0.5-2 g/kg), midazolam (0.5-1 mg/kg), and baclofen (5-10 mg/kg) did not affect spontaneous locomotor activity in a control experiment. The present results indicate that (i) ethanol may block nicotine-induced seizures in mice at doses that do not alter locomotor activity and (ii) the anti-seizure effects of ethanol depend on blood ethanol levels and are comparable to those exerted by the GABAA positive modulator midazolam.
Korkosz
Agnieszka
A
Department of Pharmacology, Institute of Psychiatry and Neurology, Sobieskiego 9 Street, PL-02957 Warsaw, Poland.
Zatorski
Pawel
P
Taracha
Ewa
E
Plaznik
Adam
A
Kostowski
Wojciech
W
Bienkowski
Przemyslaw
P
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D001418:Baclofen / Q000494:pharmacology* / Q000627:therapeutic use; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004830:Epilepsy, Tonic-Clonic / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D000431:Ethanol / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D018682:GABA Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008874:Midazolam / Q000494:pharmacology* / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine
D000927:Anticonvulsants; D002492:Central Nervous System Depressants; D018682:GABA Agents; D000431:Ethanol; D009538:Nicotine; D001418:Baclofen; D008874:Midazolam