Corticosteroids enhance convulsion susceptibility via central mineralocorticoid receptors

Recently, interest in the roles of central nervous system mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) has increased. In vitro results have implicated MR in the enhancing effects of corticosteroids and GR in the suppressing effects of corticosteroids on hippocampal excitability. Although indirect evidence exists suggesting that opposing actions of central MR and GR occur in vivo, direct evidence from studies employing receptor agonists and antagonists is only beginning to emerge. Work in our laboratory suggests that increased corticosterone levels are associated with increased severity of ethanol, pentobarbital, and diazepam withdrawal. Further work with chemical convulsants suggests that MR mediate excitatory effects of corticosteroids on convulsion susceptibility. The circadian rhythm in convulsion susceptibility varies with the circadian rhythm of plasma corticosterone levels and MR binding. The types of convulsions affected by manipulations of MR activity are believed to be of limbic origin, suggesting that limbic convulsions may be alleviated by the use of specific MR antagonists. In addition, because MR are substantially bound at rest and maximally occupied during the circadian peak in corticosteroid levels and during stressor exposure, these receptors are implicated in the maintenance of and in changes in the arousal state of animals.