Abstracts

Although progestins have long been known to mediate seizure processes, the brain areas and mechanisms for progestins[apos] anti-seizure effects are not entirely understood. The present studies investigated whether progesterone (P)[rsquo]s anti-seizure effects involve actions at intracellular progestin receptors (PRs), GABA[sub]A[/sub] receptors, and/or NMDA receptors in the hippocampus of female rats. Rats were administered progesterone or vehicle followed 1 hour later by receptor antagonists or vehicle, as described below. Two hours following antagonist or vehicle administration, seizures were induced by pentylenetetrazole (70 mg/kg). Rats were monitored for tonic-clonic seizures for 10 minutes.
[underline]Experiment 1[/underline]: Ovariectomized (ovx) rats were administered P (500 [mu]g, SC) or vehicle (sesame oil) and/or the PR antagonist, RU38486 (10 [mu]g), or vehicle ([szlig]-cyclodextran) infusions to the hippocampus. [underline]Experiment 2[/underline]: Ovx rats were administered P (500 [mu]g, SC) or vehicle (sesame oil) and/or the GABA[sub]A[/sub] receptor antagonist, bicuculline (100 ng), or vehicle (saline) infusions to the hippocampus. [underline]Experiment 3[/underline]: Ovx rats were administered P (500 [mu]g, SC) or vehicle (sesame oil) and/or the NMDA receptor antagonist, MK801 (200 ng), or vehicle (saline) to the hippocampus. [underline]Experiment 1:[/underline] Rats administered P had significantly longer latencies to, and fewer incidences of, tonic-clonic seizures compared to vehicle-administered rats. Administration of RU38486 to the hippocampus of P-primed rats attenuated P[rsquo]s anti-seizure effects. There were no intrinsic effects of RU38486 on ictal activity.
[underline]Experiment 2:[/underline] P administration decreased ictal activity of ovx rats. P-primed rats infused with bicuculline had increased ictal activity compared to P-administered rats infused with vehicle. Bicuculline infusions alone did not alter seizures. [underline]Experiment 3:[/underline] Administration of P decreased seizures of ovx rats. Infusions of MK801 to the hippocampus of P-primed rats attenuated P[rsquo]s anti-seizure effects. Infusions of MK801 alone did not alter ictal activity of rats. Together these data suggest that P[rsquo]s anti-seizure effects involve actions at PRs, GABA[sub]A[/sub] and NMDA receptors in the hippocampus. (Supported by The Epilepsy Foundation of America and The National Science Foundation (98-96263, 03-16083).)