1. ¹The Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia
2. ²The Department of Psychiatry, St Vincent's Hospital, Australia
3. ³The Department of Pharmacology, The University of Melbourne, Australia
4. ⁴The Department of Anatomy, The University of Melbourne, Australia
5. ⁵The Department of Neurology, The Royal Melbourne Hospital, Australia

Correspondence: Dr TJ O'Brien, The Department of Medicine, The Royal Melbourne Hospital, Royal Parade, Parkville, 3050, Victoria, Australia. Tel: +613 8344 3260; Fax: +613 9348 2254; E-mail: obrientj@unimelb.edu.au

Received 19 October 2004; Revised 23 December 2004; Accepted 20 January 2005; Published online 16 March 2005.

Abstract

Mesial temporal lobe epilepsy (MTLE) is associated with high rates of depression and anxiety. A bidirectional causal relationship has been suggested, with these psychiatric comorbidities themselves enhancing epileptogenesis, possibly via hypercortisolemia. We examined the effects on epileptogenesis of chronic supplementation with low-dose corticosterone (CS) in the electrical amygdala kindling rat model. Adult Wistar rats were ovariectomized and implanted with bipolar electrodes into the left amygdala. After 1 week recovery, one group (n=7) had CS (3 mg/100 ml—approx. 4.5 mg/kg/day) and a control group saline (n=7) added to their drinking water, and both groups underwent twice daily electrical stimulations. Rats were culled 2 weeks after reaching the fully kindled state. A stereological optical fractionator technique was used to estimate the number of CA1 pyramidal cells in the hippocampus ipsilateral to the stimulations. Fewer stimulations were required in the CS-supplemented rats than in controls to reach the fully kindled state (32 vs 81, p<0.03, Student's t-test) and the first Class V seizure (14 vs 57, p<0.05). The mean after-discharge length was greater in the CS group (p=0.03, repeated measures analysis of variance). There was no difference in the mean number of CA1 neurons (1.05 10⁵ vs 1.04 10⁵, p=0.98). These data demonstrate that low-dose CS enhances epileptogenesis in this model of MTLE. This provides support for the hypothesis that chronic hypercortisolemia, as a result of stress, anxiety, and/or depression, may facilitate the development and progression of epilepsy in patients with MTLE. The lack of difference in hippocampal CA1 neurons indicates that the mechanism does not primarily involve pyramidal cell loss.