Abstracts

We have previously demonstrated that low-dose corticosterone (CS) supplementation, as a model of the effect of chronic stress/depression, accelerates epileptogenesis in the amygdala kindling rat model of temporal lobe epilepsy (TLE). This study examined the contributions to this effect of subtypes of glucocorticoid receptors, MR (high-affinity) and GR (low-affinity). Adult rats were ovariectomized and implanted with a bipolar electrode into the left amygdala. Five experimental groups were studied: Water-control (n=5), CS (6mg/100ml in drinking water) treated (n=4), Mifepristone (GR-antagonist, 25mg/kg) + CS (n=5), Spironolactone (MR antagonist, 50mg/kg) + CS (n= 4), and Mifepristone (25mg/kg) + Spironolactone (50mg/kg) + CS treated (n=5). Rats were injected subcutaneously with vehicle (Groups 1 and 2) or the relevant antagonist in vehicle (Groups 3-5) twice daily for the entire kindling period. Kindling was begun two days after initiation of treatment. The experimental groups differed significantly in time to reach the [apos]fully kindled state[apos] (p=0.04, Kruskal-Wallis ANOVA). The CS-treated group kindled faster than either the water-treated control group or the Mife+Spiro+CS group (p[lt]0.05). No significant differences were found when either antagonist was given alone compared to CS- or water-treated controls. The data implicate both high affinity (MR) and low affinity (GR) glucocorticoid receptors in the mechanism by which low-dose CS accelerates kindling epileptogenesis. This may have implications for understanding the potential effects of chronic stress and depression in initiating and/or exacerbating TLE.