Abstracts

We have previously demonstrated that low-dose corticosterone (CS) supplementation, used 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 the subtypes of glucocorticoid receptors: mineralocorticoid (MR, high-affinity for CS) and glucocorticoid (GR, low-affinity for CS)., Female Non-Epileptic Control rats 10-13 weeks of age were ovariectomized and implanted with a bipolar electrode into the left amygdala. Five experimental groups were studied: Water-control (n=6), CS treated (n=6), CS + Mifepristone (Mif - GR-antagonist, 25mg/kg sc, n=7), CS + Spironolactone (Spir - MR antagonist, 50mg/kg, n= 5), and CS + Mif (25mg/kg) + Spir (50mg/kg) (n=6). Corticosterone was dissolved in drinking water (6mg/100 ml) and administered [italic]ad libitum [/italic](groups 2-5) throughout the kindling period. 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. Rapid Amygdala Kindling (RAK), which began two days after initial treatment, consisted of 10 sec bursts of 400[mu]A every 15-20 mins, with up to 24 stimulations per day., Groups differed significantly in the number of stimulations required to reach the [apos]fully kindled state[apos] defined as five Class V seizures on the Racine scale (p=0.04, Kruskal-Wallis ANOVA). The CS-treated group kindled faster than either the water-treated control group (p[lt]0.05) or either of the three CS+antagonist groups (p[lt]0.10). No significant differences were found between the any of the CS+antagonist groups and the 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., (Supported by an NHMRC project grant (400088), and a NARSAD Independent Investigator Award (TOB).)