Vagus nerve stimulation has antidepressant potential in the kainic acid model for temporal lobe epilepsy

Abstract

Aim : Depression represents one of the most common and disabling comorbidities in epilepsy patients. There is a growing consensus that both disorders have a common neurobiological cause. Vagus nerve stimulation (VNS) is an add-on treatment for patients with refractory epilepsy or depression. Both the mechanism of this comorbidity and the mechanism of action of VNS are poorly understood. In this study, we investigated the antidepressant potential of VNS in the kainic acid (KA) model for temporal lobe epilepsy (TLE). Methods : Male Sprague Dawley rats (n=29) were implanted with a cuff-electrode around the left vagus nerve. One week after surgery, half of the animals were subjected to a kainic acid KA-induced status epilepticus (SE). The other half of the animals were injected with saline (Sal). Both groups were subdivided in a VNS-treated group and a SHAM-treated group, yielding 4 experimental groups: Sal-SHAM (n=8), Sal-VNS (n=7), KA-SHAM (n=7), KA-VNS (n=7). Five weeks post-SE, the behavioral equivalent of anhedonia (i.e. inability to experience pleasure), was assessed using the saccharin preference test (SPT). To control for loss of taste due to KA-induced SE and subsequent neuronal loss, a quinine preference (of aversion) test (QPT) was performed. Both VNS groups (Sal-VNS and KA-VNS) received 2 weeks of therapeutic VNS, both SHAM groups received SHAM treatment. After this period, SPT and QPT were performed again in the same animals. Results : KA rats showed a significant reduction of taste preference towards saccharin compared to Sal rats (25% vs. 95 %, p < 0.001). No difference in aversion towards quinine was found. Two weeks of VNS significantly increased saccharin preference (SP) in the KA-VNS group (14% to 60% p < 0.001), while no difference could be demonstrated in SHAM-treated animals of the KA group. VNS had no influence on the QPT. There were no significant changes of SP in Sal-VNS and Sal-SHAM group. Conclusion : KA-injected epileptic rats display signs of anhedonia based on the SPT compared to non-epileptic control rats. Two weeks of VNS significantly reduced this anhedonia, suggesting an antidepressant effect of VNS in this rodent model for TLE.