Vagus nerve stimulation (VNS) is effective in a rat model of antidepressant action.

Depression is a common but debilitating illness that afflicts a large population and costs the US economy a staggering $40 billion dollars per year. Clinical studies have demonstrated that vagus nerve stimulation (VNS) is an effective treatment for medication-resistant depression. Understanding VNS's antidepressant mechanisms is key to improving the therapy and selecting the best surgical candidates, and demonstration that VNS is effective in a validated test of antidepressant activity allows us to elucidate these mechanisms in a cost-effective manner. In the present study, Wistar Kyoto rats were implanted with a cuff electrode on the left cervical vagus nerve. The next day, they were placed into a water-filled Plexiglas cylinder for 15 min. After this forced-swim session, one of three treatment conditions were administered over 4 consecutive days: 30 min per day of continuous VNS, 10 mg/kg of desipramine twice per day, or three daily electroconvulsive shocks (ECS). Yoked controls underwent sham procedures, but received no treatment. On the fourth day, the rats were given a 5-min, videotaped swim test. A blinded observer used the videotape to calculate the percentage of time that the rats were immobile (an index of depression) during the swim test. VNS significantly reduced immobility time as compared to unstimulated controls, indicating good antidepressant efficacy. This reduction did not differ statistically from that obtained from rats treated with either desipramine or ECS, two standard antidepressant treatments. These results indicate that VNS is an effective antidepressant in the forced-swim test, allowing us to now investigate possible therapeutic mechanisms.

Right-sided vagus nerve stimulation reduces generalized seizure severity in rats as effectively as left-sided.

As currently utilized, vagus nerve stimulation (VNS) is applied to the cervical trunk of the left vagus nerve to suppress seizures clinically. Demonstration that VNS can also reduce seizure severity when electrodes are placed on the right cervical vagus nerve in rats would provide empirical evidence that the antiepileptic effects of VNS are not an exclusive property of the left vagus nerve. Rats were implanted with a custom cuff electrode on either the left or right cervical vagus nerve. Two days later, continuous VNS was begun in half the rats with left-sided and half with right-sided electrodes. The remaining rats were connected to the stimulator, but did not receive VNS. After 30s, pentylenetetrazole (PTZ) was administered systemically and seizures were rated by a blinded observer. The PTZ test was repeated two days later, with VNS administered to the previously unstimulated rats, while the others received no stimulation. VNS significantly reduced the severity of PTZ-induced seizures in rats regardless of the side of stimulation as compared to their no-VNS (control condition) seizure severity. No significant differences in efficacy existed based on the side of stimulation. These results indicate that right-sided VNS in rats is just as effective as left-sided VNS, suggesting that fibers necessary for seizure suppression are not unique to the left vagus nerve.