The Acute Anticonvulsant Effects of Deoxycorticosterone in Developing Rats: Role of Metabolites and Mineralocorticoid-Receptor Responses

The study investigated the acute anticonvulsant effects of deoxycorticosterone (DOC) in 15-day-old rats, focusing on the roles of its metabolites and mineralocorticoid-receptor responses. The results indicated that agonists of mineralocorticoid receptors increased seizure latency and sometimes completely suppressed seizures. Spironolactone, a mineralocorticoid-receptor antagonist, blocked the anticonvulsant effects of a nonsedating dose of DOC, suggesting the involvement of these receptors. Finasteride, which inhibits DOC metabolism, partially blocked DOC's protective effects, indicating the contribution of metabolites. Metabolites like dihydrodeoxycorticosterone and tetrahydrodeoxycorticosterone, which modulate the GABA A receptor, also blocked seizures. The study concluded that both DOC and its metabolites contributed to anticonvulsant effects through interactions with various receptors.