The effect of progesterone on the seizures of the lithium-pilocarpine model in the female ovariectomized rat: an investigation on behavioral, biochemical and the activity of glutamine synthetase enzyme

Epileptic seizures, during menstrual cycle, are mostly due to low level of progesterone. Furthermore, astrocytes influence brain excitability. Therefore, this study investigates the anticonvulsive effect of progesterone on convulsions, glutamate and GABA content and the involvement of the astrocytes through glutamine synthetase (GS) enzyme.

Female Wistar rats (n = 120) were assigned in six experimental groups including; naïve control, ovariectomized control, pilocarpine, progesterone treatment groups (0.2, 2, and 20 mg/kg). Lithium-Pilocarpine model was used to induce convulsions and the behavior was evaluated during one hour after pilocarpine injection. Progesterone, with low, medium and high doses was daily administered for five days. Following five or thirty days, the brains were dissected and the hippocampal glutamate, GABA and the activity of glutamine synthetase were measured.

Latency to convulsions decreased (184%), only in high-dose (HD) progesterone group, while the duration of seizures decreased in low, medium and high (105, 59, and 265%) doses of progesterone. In the five-day sacrificed animals, the GC activity decreased (164%) in HD progesterone treated group. In the thirty-day groups, GABA increased (176%) due to pilocarpine and decreased following the progesterone treatment in the low, medium and high (106, 70, and 64%) doses.

It is concluded that progesterone administration has anticonvulsive (concentration dependent) effects, and changes the glutamate and GABA content and astrocytic GS activity.