Abstracts

Rationale: Psychiatric disorders such as depression are present in a high proportion of epilepsy patients, including those with mesial temporal lobe epilepsy. Evidence suggests that these psychiatric disorders may predate the onset of epilepsy, suggesting a causal role. We have previously demonstrated that corticosterone supplementation, used as a model of chronic stress/depression, accelerates epileptogenesis in the amygdala kindling rat model of limbic epilepsy (Taher et al, Neuropsychopharmacology, 2005). The current study extended this to examine whether repeated application of a realistic stress, physical restraint, could similarly influence the development of experimental epilepsy. Methods: Female Non-Epileptic Control rats 10-13 weeks of age were implanted with a bipolar electrode into the left amygdala, and, following recovery, were randomly assigned into stressed (n=18) or non-stressed (n=19) groups. Rats underwent either conventional amygdala kindling (2 electrical stimulations per day) until 5 Class V seizures had been experienced (‘fully kindled’) or sham kindling. Stressed rats were exposed to 30 minutes restraint immediately prior to each kindling stimulation, whereas Non-stressed rats received control handling prior to stimulation. At appropriate intervals during the kindling process, blood samples were taken immediately after restraint stress to assess stress responsivity. Results: Restraint stress increased circulating corticosterone levels (pre-stress: 122±17 ng/ml; post-stress: 632±33 ng/ml), and no habituation over repeated episodes of restraint was observed. Stressed rats reached the fully kindled state with significantly fewer stimulations than Non-stressed rats (20±1 vs 30±3 stimulations; p=0.015; ANOVA). Furthermore, the length of each electrographic seizure was significantly longer in stressed rats (p=0.001; repeated measures ANOVA). The development of epilepsy had no effect on the corticosterone response to stress throughout the kindling period. Conclusions: Chronic stress accelerates the development of experimental limbic epilepsy, an effect which may be related to elevated corticosterone levels. This may have implications for understanding the effects of chronic stress and depression in initiating and/or exacerbating Mesial Temporal Lobe Epilepsy in humans.