Increased hippocampal extracellular noradrenaline contributes to the anticonvulsant effect of VNS in the focal pilocarpine rat model for limbic seizures.

Introduction: Vagus nerve stimulation (VNS) is a treatment for refractory epilepsy. The aim of this study is to unravel the potential mechanism of action by screening of the VNS-induced changes in hippocampal neurotransmitters in relation to the limbic seizure suppressing action of this treatment in an animal model for limbic seizures.
Methods: During VNS in male Wistar rats, intrahippocampal microdialysis was performed to monitor extracellular noradrenaline, dopamine, serotonin and GABA concentrations and to evoke seizures by administration of pilocarpine. The effect of VNS on seizure activity was assessed using video-EEG. The role of VNS-induced increases in hippocampal noradrenaline was evaluated by blocking hippocampal alpha2-receptors.
Results: VNS significantly increased hippocampal noradrenaline levels by 69 ± 16% above baseline levels. VNS also increased the latency between pilocarpine infusion and the onset of epileptiform discharges, and reduced seizure duration and severity. A strong positive correlation was found between the noradrenergic and anticonvulsant effects of VNS. Blockade of hippocampal alpha2-receptors reversed the seizure-suppressing effect of VNS.
Conclusion: VNS induces increases in extracellular hippocampal noradrenaline, which are at least partly responsible for its seizure-suppressing effect in a model for limbic seizures, and constitute a potential biomarker for the efficacy of VNS in temporal lobe epilepsy.