Abstracts

It has long been noted that temporal lobe epilepsy (TLE) patients have high rates of depression and anxiety. Recently it has been suggested that these psychiatric co-morbidities may play a role in enhancing epileptogenesis in TLE, with one possible mechanism being an effect of the associated hypercortisolaemia. The electrical amygdala-kindling model is one of the best-studied and validated models of TLE. We compared the effects of chronic supplementation with low-dose corticosterone on the number of stimulations required to reach the fully kindled state in rats undergoing electrical amygdala kindling. Sixteen week old non-epileptic wistar rats were ovariectomized and implanted with a bipolar electrode into the left amygdala complex. After a one week recovery period one group of rats (n=7) had corticosterone (CS; 3mg/100mls [ndash] approx. 4.5 mg/kg/day) added to their drinking water while in the control group saline (0.9 mg/100mls) was added. Twice daily electrical stimulations (200 mA, 1 msec duration, 50 Hz for 1 second) were applied via the bipolar electrode. With this technique, initially the stimulations result in no behavioral effects, but after repeated stimuli the rats start having increasingly prominent seizures. The number of stimulations required to reach the fully kindled state (defined as five Class V seizures) was compared between the two treatment groups. Fewer stimulations were required in the CS supplemented rats than in controls to reach the fully kindled state (32 vs 81, p[lt]0.03, Student [italic]t[/italic]-test) and the first Class V seizure (14 vs 57, p[lt]0.05, Student [italic]t[/italic]-test). There was a trend for less stimulations to the first seizure and the first convulsive seizure (both, p=0.05). The mean length of the after discharges (electrographic seizures) was significantly greater in the corticosterone treated group (p=0.03, repeated measures ANOVA). These data demonstrate that low-dose CS supplementation enhances epileptogenesis in the amygdala kindling rat model of TLE. This provides support for the hypothesis that chronically elevated cortisol levels, as a result of stress, anxiety and/or depression, may facilitate the development and progression of epilepsy in patients with TLE.