The effects of ACTH and adrenocorticosteroids on seizure susceptibility in 15-day-old male rats.
Infantile spasms are generalized convulsive seizures seen in the first year of life. They respond poorly to conventional anticonvulsants, but are often controlled by adrenocorticotropic hormone (ACTH) therapy. Other childhood seizures are also responsive to ACTH. The present study tested the effects of ACTH and related adrenocorticosteroids in prepubertal, 15-day-old rats. Compounds were tested against minimal (scMET) and maximal (MMT) pentylenetetrazol seizures, maximal electroconvulsive shock (MES) seizures, and hippocampal kindled seizures. ACTH had no significant anticonvulsant effects against any type of seizure. Several of the adrenocorticoid hormones, however, had strong anticonvulsant effects. Deoxycorticosterone (DOC) and progesterone (P4) both significantly suppressed scMET, MMT, and MES seizures 15 min after s.c. injection. DOC and P4 also shortened hippocampal discharge duration in the kindling model, and DOC, but not P4, suppressed the kindled convulsion. Aldosterone and corticosterone were effective against scMET seizures, and aldosterone was effective against MMT seizures. Dexamethasone and dihydroepiandrosterone had no anticonvulsant activity. These findings indicate that the adrenal steroid precursors, DOC and P4, have a broad spectrum of anticonvulsant activity in animal seizure models. They may play a role in mediating the anticonvulsant effects of ACTH in human infants.
Edwards
Heather E
HE
Bloorview Epilepsy Research Program, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
Vimal
Sutha
S
Burnham
W McIntyre
WM
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D004567:Electrodes, Implanted; D004597:Electroshock; D005552:Forelimb / Q000503:physiopathology; D005938:Glucocorticoids / Q000494:pharmacology; D006624:Hippocampus / Q000503:physiopathology; D007696:Kindling, Neurologic; D008297:Male; D010433:Pentylenetetrazole; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*
D005938:Glucocorticoids; D003900:Desoxycorticosterone; D003687:Dehydroepiandrosterone; D000450:Aldosterone; D011374:Progesterone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D010433:Pentylenetetrazole