Role of nitric oxide in the anticonvulsive effect of progesterone

Described here is an investigation of the potential interaction of the nitric oxide signaling pathway with the anticonvulsant effects of progesterone. In ovariectomized Swiss mice, the threshold for seizures induced by intravenous infusion of pentylenetetrazole was determined after treatment with progesterone (25, 50, or 75 mg/kg, given subcutaneously 6 h before seizure testing) or vehicle. Progesterone induced significant anticonvulsive activity at moderate (50 mg/kg) and high (75 mg/kg) doses. This effect of progesterone was abolished by the NO precursor compound l-arginine (200 mg/kg). Moreover, when subeffective doses of progesterone (25 mg/kg) and the NO synthase inhibitor Nω-nitro-l-arginine methyl ester (10 mg/kg) were injected, a strong anticonvulsant effect was observed. These findings suggest a potential role for NO signaling as an anticonvulsant target in females.