Vagus nerve stimulation suppresses pilocarpine-induced limbic seizures and increases hippocmapal extracellular noradrenalin concentration

RATIONALE:
Vagus nerve stimulation (VNS) is an adjunctive treatment for patients with refractory epilepsy. Increased release of noradrenalin in the hippocampus, caused by altered activity in the locus coeruleus, has been advanced as a possible mechanism of action of VNS in epilepsy. The aim of this study was to simultaneously evaluate the effect of VNS on pilocarpine-induced limbic seizures and on hippocampal EC neurotransmitter concentrations in rats.
METHODS:
Both control and stimulated rats were implanted with a stimulation electrode around the left vagus nerve. Depth EEG electrodes and a microdialysis probe were stereotactically implanted in the left hippocampus. One week later, limbic seizures were evoked by intrahippocampal administration of pilocarpine via the microdialysis probe. In the stimulated group, VNS was initiated 2 h prior to pilocarpine administration and continued until the end of the experiment. Behavioural changes indicative of seizure activity were scored. Hippocampal depth EEG and hippocampal extracellular noradrenalin, dopamine, serotonin and GABA concentrations were monitored.
RESULTS:
In the stimulated group, behavioural seizure scores (3.0 +/- 0 vs. 14.5 +/- 4.5), the number of electrographic seizures (no seizures vs. 10 +/- 5 seizures) and the duration of spiking on hippocampal EEG (37 +/- 1 min vs. 110 +/- 40 min) were profoundly reduced compared to control. Moreover, VNS resulted in a rapid and sustained increase in hippocampal extracellular noradrenalin concentration (255 +/- 45%) but had no effect on hippocampal dopamine, serotonin and GABA levels.
CONCLUSIONS:
VNS increases hippocampal extracellular noradrenalin concentration, and attenuates pilocarpine-induced limbic seizures. Additional experiments will be performed to clarify the involvement of increased hippocampal noradrenalin in the mechanism of action of VNS in epilepsy.