3alpha,5alpha-THP in the raphe magnus attenuates PTZ-induced myoclonic seizures

Whether progesterone (P(4)) and its metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) have anti-seizure effects through actions in the raphe magnus (NRM) was investigated. Ovariectomized, Long-Evans rats with unilateral implants into the NRM of P(4) or its metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) had a significantly lower incidence of myoclonic seizures and less EEG activity following pentylenetetrazol (PTZ; 70 mg/kg, IP) administration than did rats with control implants. Progestin implants that missed the NRM were not effective at reducing ictal activity. Following P(4) implants to the NRM levels of P(4), and following P(4) and 3alpha,5alpha-THP implants to the NRM, 3alpha,5alpha-THP levels in the ventral hindbrain were increased above those seen in rats with control implants. These data suggest that progestins' anti-seizure effects in the NRM may be involve actions of 3alpha,5alpha-THP.