Effects of neurosteroids on kainate-induced seizures, neurotoxicity and lethality in mice.
In the present study we examined effects of some neurosteroids on the kainate-induced seizures, lethality and neurotoxicity in mice. We found that 5 alpha-pregnan-3 alpha-ol-20-one (allopregnanolone; 10 and 20 mg/kg) markedly elevated CD50 for kainate-induced convulsions, whereas 5 beta-pregnan-3 alpha-ol-20-one, 5 alpha-pregnan-3 alpha-ol-11,20-dione, 5 alpha-androstan-3 alpha-ol-17-one, dehydroepiandrosterone sulfate, pregnenolone sulfate and aminosteroid (U-107) were ineffective in that test. Furthermore, 5 alpha-pregnan-3 alpha-ol-20-one (5-20 mg/kg), 5 beta-pregnan-3 alpha-ol-20-one (20 mg/kg) and 5 alpha-androstan-3 alpha-ol 17-one (10 and 20 mg/kg) decreased, while dehydroepiandrosterone sulfate (25 and 50 mg/kg) and pregnenolone sulfate (25 mg/kg) elevated the kainate-induced lethality in mice. A histological analysis showed that kainate caused a dose-dependent neuronal loss of CA1 and CA3 hippocampal fields. Of the neurosteroids tested, only allopregnanolone attenuated the kainate-induced neurotoxicity. The above data indicate that neurosteroids exert moderate effects on seizures and neurotoxic effects of kainate. On the other hand, neurosteroids with a GABAA receptor agonistic or antagonistic activity decrease or increase, respectively, the kainate-evoked lethality.
Leśkiewicz
M
M
Department of Endocrinology, Polish Academy of Sciences, Kraków, Poland.
Budziszewska
B
B
Jaworska-Feil
L
L
Lasoń
W
W
D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism / Q000633:toxicity*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007608:Kainic Acid / Q000378:metabolism / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013256:Steroids / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid; D018092:Kainic Acid Receptors; D013256:Steroids