Finasteride inhibits the progesterone-induced spike-wave discharges in a genetic model of absence epilepsy.
Previously, it was found that progesterone aggravates spike-wave discharges (SWD) in WAG/Rij rats in a nongenomic way. In order to elucidate whether the regulatory effect of progesterone depends on its conversion to allopregnanolone, the effect of finasteride, a 5alpha-reductase inhibitor, on progesterone-induced increase in SWD was studied in the same model for absence epilepsy. Progesterone (10 and 20 mg/kg ip) dose-dependently increased the number of SWD (by 54% and 97%, respectively) during the first hour postinjection. Pretreatment of rats with finasteride (50 mg/kg sc) blocked the progesterone-induced enhancement of SWD. Finasteride alone had no effect on the number of SWD, up to 24 h following its administration. It is concluded that finasteride blocked the progesterone-induced increase in SWD, which indicates that this action of progesterone is mediated by its neuroactive metabolite allopregnanolone.
van Luijtelaar
Gilles
G
NICI, Biological Psychology, University of Nijmegen, The Netherlands. luijtelaar@nici.kun.nl
Budziszewska
Bogusława
B
Tetich
Magdalena
M
Lasoń
Władysław
W
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000200:Action Potentials / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004832:Epilepsy, Absence / Q000235:genetics* / Q000503:physiopathology; D018120:Finasteride / Q000494:pharmacology*; D008297:Male; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D011374:Progesterone; D018120:Finasteride; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase