Type I corticosteroid receptors modulate PTZ-induced convulsions of withdrawal seizure prone mice.
Corticosteroids have been shown to modulate convulsion expression in humans and animals. It is hypothesized that type I corticosteroid receptors mediate the excitatory effects of corticosteroids in vivo based on low-dose efficacy of corticosterone, and differential effects of mineralocorticoids vs. glucocorticoids on convulsions. In the present experiments, the effects of altering corticosterone levels, and the role of the type I receptor in mediating these effects, were examined using pentylenetetrazol (PTZ)-induced convulsions in ethanol withdrawal seizure prone (WSP) mice. It was hypothesized that stimulation of type I receptors partially mediates the expression of tonic hindlimb extensor (THE) convulsions produced by PTZ. Aminoglutethimide, a steroid synthesis inhibitor, increased latencies to PTZ-induced THE. This anticonvulsant effect was reversed by corticosterone and the type I agonist, deoxycorticosterone (DOC), but not by the type II agonist, dexamethasone. Furthermore, two type I receptor antagonists, spironolactone and RU26752, increased latencies to PTZ-induced THE, suggesting that they have anticonvulsant action. In summary, the results of these experiments suggest that type I corticosteroid receptors are important for expression of PTZ-induced convulsions.
Roberts
A J
AJ
Department of Medical Psychology, Oregon Health Sciences University, Portland 97201.
Crabbe
J C
JC
Keith
L D
LD
D000616:Aminoglutethimide / Q000494:pharmacology; D000818:Animals; D003900:Desoxycorticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004198:Disease Susceptibility; D000431:Ethanol / Q000009:adverse effects*; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D011930:Reaction Time / Q000187:drug effects; D011987:Receptors, Steroid / Q000502:physiology*; D012640:Seizures / Q000209:etiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D011987:Receptors, Steroid; D000616:Aminoglutethimide; D000431:Ethanol; D003900:Desoxycorticosterone; D003907:Dexamethasone; D010433:Pentylenetetrazole