Dexamethasone and Hormones Related to the Hypothalamic-Pituitary-Adrenal Axis Modulate Inherited Neocortical Spindling in DBA/2J Mice

Abstract

The role of dexamethasone and hormones related to the hypothalamic-pituitary-adrenal (HPA) axis (corticotropin-releasing factor, adrenocorticotropic hormone, corticosterone) in the control of the spike-and-wave spindling episodes (S&W) which can be spontaneously recorded in the electrocorticogram (ECoG) of DBA/2J mice was investigated. Both dexamethasone and hormones related to the HPA axis consistently reduced the S&W in DBA/2J mice. Cycloheximide (a protein synthesis inhibitor) pretreatment significantly delayed the reducing effect of dexamethasone on the S&W in mice. After a transitory decrease, the glucocorticoid receptor antagonist RU-38486 induced a dramatic increase in the rate of the S&W episodes. In addition, mice treated with RU-38486 for 4 days showed a significant increase in the S&W 24 h after the 4th treatment. Our results indicate that dexamethasone as well as hormones related to the HPA axis are able to modulate the S&W in DBA/2J mice, suggesting that this effect may be bound to corticosteroid activity. The time lag (30-60 min) which is necessary for revealing the reducing influence of dexamethasone on the S&W in mice and the influence exerted by cycloheximide on dexamethasone activity support the hypothesis that the effect induced by dexamethasone may be at least in part dependent on genomic mechanisms.