5 alpha-Pregnan-3 alpha-ol-20-one blocks nicotine-induced seizures and enhances paired-pulse inhibition.
5 alpha-Pregnan-3 alpha-ol-20-one (3 alpha-OH-DHP) blocked seizures induced by nicotine (4 mg/kg, i.p.) in C3H male mice with an ID50 of 2.37 +/- 0.66 mg/kg (average +/- 95% confidence limit). This steroid (1 microM) also increased paired-pulse inhibition in the hippocampus approximately 40% after 50 min exposure; nicotine (200 microM) partially reversed this effect. Since nicotine and 3 alpha-OH-DHP may have opposite effects on endogenous inhibitory systems, it is proposed that nicotine-induced seizures may involve a disinhibitory mechanism and that 3 alpha-OH-DHP protects against seizures by preventing disinhibition.
Luntz-Leybman
V
V
Institute for Behavioral Genetics, University of Colorado, Boulder 80309.
Freund
R K
RK
Collins
A C
AC
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004558:Electric Stimulation; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009538:Nicotine / Q000037:antagonists & inhibitors*; D011280:Pregnanolone / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*
D000927:Anticonvulsants; D009538:Nicotine; D011280:Pregnanolone