The acceleration of amygdala kindling epileptogenesis by chronic low-dose corticosterone involves both mineralocorticoid and glucocorticoid receptors

We have previously demonstrated that tow-dose corticosterone (CS) administration, used as a model of the effect of chronic stress, accelerates epileptogenesis in the etectrical amygdala kindling rat model. of temporal lobe epilepsy (TLE). This current study examined the relative contributions to this effect of mineralocorticoid (MR) and glucocorticoid (GR) subtypes of glucocorticoid receptors. Female non-epileptic wistar rats 10-13 weeks of age were implanted with a bipolar electrode into the left amygdala. Five treatment groups were subjected to rapid amygdala kindling: water-control (n = 9), CS treated (6 mg/100 ml. added to drinking water; n = 9), CS+spironolactone (MR antagonist, 50 mg/kg sc; n = 9), CS+mifepristone (GR antagonist, 25 mg/kg sc; n = 9), and CS+both antagonists (n = 7). Rats were injected with vehicle or the relevant antagonist twice daily for the entire kindling period. Experimental groups differed significantly in the number of stimulations required to reach the 'fully kindled state' (Racine, 1972) ANOVA, F-(4,F-38) = 2.73, p = 0.04). Amygdala kindling was accelerated in the CS-treated group compared with water controls (mean stimulations for full kindling: 45.2 vs. 86.5, p < 0.01). This acceleration was inhibited by both the MR and GR antagonist treatments (mean stimulations: 69.6 and 70.4, p = 0.04 and 0.04 vs. CS group, respectively), with the kindling rates in these groups not significantly different from water-treated subjects (p = 0.26 and 0.29, respectively). The kindling rates in the MR and GR antagonist treatment groups did not significantly differ from each other (p = 0.93), nor from the combined treatment group (mean stimulations: 62.8, p = 0.59 and 0.54, respectively). This study demonstrates that activation of both high-affinity (MR) and tow-affinity (GR) glucocorticoid receptors are involved in mediating CS-induced acceleration of amygdala kindling epileptogenesis. (C) 2007 Elsevier Ltd. All rights reserved.