Acute vagus nerve stimulation increases norepinephrine levels in the cerebrospinal fluid of Beagle dogs

Vagus nerve stimulation (VNS) is an effective treatment for refractory epilepsy, but it remains unclear which factors determine the patient’s responsiveness and which are the optimal stimulation parameters to use. Several studies in rodents show that the locus coeruleus(LC)–norepinephrine(NE)system plays an important role. This study investigated the effects of two VNS paradigms on the dopamine (DA), serotonin (5HT) and NE levels in the cerebrospinal fluid (CSF) of normal dogs. Ten dogs were implanted with a Cyberonics® pulse generator and helical electrodes around the left vagosympathetic trunk. A cross-over study started 1 month after implantation. CSF was collected immediately after 3 different conditions (1 hour of sham, rapid-cycling and microburst VNS) and a wash out period of 1 week between different conditions was respected. The concentration of monoamines in the CSF was measured by microbore liquid chromatography with electrochemical detection. Statistical analysis was based on a mixed model with dog as random effect; the two VNS regimes were compared pairwise with sham using Dunnett’s multiple comparisons technique at a global significance level of 5%. Acute rapid-cycling VNS did not cause significant changes in DA, 5HT and NE levels in the canine CSF. Acute microburst VNS caused a significant increase (mean=72.9%) in the NE levels (p=0.05), but did not cause significant alterations in 5HT nor DA concentrations. In conclusion, acute microburst VNS results in increased CSF NE levels in the normal dog. Given the important role of the LC-NE system in the effects of VNS on experimental seizures, these results encourage further investigations into the anticonvulsive effects of microburst VNS