Dose-, time-, age-, and sex-response profiles for the anticonvulsant effects of deoxycorticosterone in 15-day-old rats

Abstract

Recently, we have shown that a single high dose of the adrenal steroid precursor hormone deoxycorticosterone (DOC) has potent anticonvulsant effects in 15-day-old rats. To better define the actions of DOC, the present study established dose-, time-, age-, and sex-response curves for the anticonvulsant actions of DOC. Methods. Dose- and time-response studies were done using two different seizure models: (1) maximal pentylenetetrazol seizures (MMT) and (2) maximal electroconvulsive shock (MES) seizures. Subsequently, age- and sex-response studies were done using MMT seizures and two different DOC doses, one low (nonsedating) and one high (sedating). Results. In dose-response studies, DOC suppressed MMT seizures with an ED(50) of about 5 mg/kg (sc). Higher doses were necessary to suppress MES seizures, where the ED(50) was about 20 mg/kg. In time-response studies, DOC's effects were rapid in onset. Complete suppression of seizures was seen by 5 min in the MES model and by 15 min in the MMT model. In developmental studies, both a low nonsedating and a high sedating dose of DOC suppressed MMT seizures in neonatal, infant, weanling, and juvenile rats of either sex. The suppressive effects of low-dose DOC were lost after puberty, however. The suppressive effects of high-dose DOC also declined after puberty, especially in males. Conclusion. DOC has significant anticonvulsant actions that occur in prepubertal, but not postpubertal subjects. DOC might have clinical importance in the future treatment of childhood seizure disorders.