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.
Frye
C A
CA
Department of Psychology, The University at Albany-SUNY, 1400 Washington Avenue, Albany, NY 12222, USA. cafrye@cnsunix.albany.edu
Muscatiello
N A
NA
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004569:Electroencephalography / Q000187:drug effects; D004831:Epilepsies, Myoclonic / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004971:Estrus / Q000378:metabolism*; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans; D012249:Rhombencephalon / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
D018756:GABA Antagonists; D011374:Progesterone; D011280:Pregnanolone; D010433:Pentylenetetrazole