EVALUATION OF THE ANTICONVULSANT PROFILE OF PROGESTERONE IN MALE AMYGDALA-KINDLED RATS

While there is clinical evidence that progesterone has anticonvulsant activity in women with complex partial seizures, previous studies on t he anticonvulsant effect of progesterone in experimental animal models are inconclusive. Moreover, the effect of progesterone on seizure par ameters in fully amygdala-kindled rats which best resemble complex par tial seizures has not been evaluated. Therefore, in the present work t he anticonvulsant effect of progesterone at doses of 10, 30, 60 and 75 mg/kg in fully amygdala-kindled male rats was studied. Only at the hi gh and sedative dose of 75 mg/kg, progesterone suppressed behavioral s eizures and afterdischarges elicited 10 min after intraperitoneal (i.p .) administration. Pretreatment with the progesterone antagonist, 17 b eta-hydroxy-11 beta-(4-dimethylaminophenyl)-17 alpha-(prop-1-ynyl)-est ra-4,9-dien-3-one (RU 38486) at the dose of 3 mg/kg did not inhibit th e anticonvulsant activity of progesterone, while pretreatment with the GABA(A) receptor antagonist, bicuculline (2 mg/kg) blocked the antico nvulsant effect of progesterone. Neither RU 38486 nor bicuculline had any effect on the seizure parameters. These findings suggest that only at large and sedative doses, progesterone has some anticonvulsant act ivity in male amygdala-kindled rats which may be partly mediated via t he GABA, receptor complex interaction. (C) 1998 Elsevier Science B.V. All rights reserved.