Abstracts

EFFECTS OF VAGUS NERVE STIMULATION ON EXTRACELLULAR SEROTONIN CONCENTRATION IN DORSAL RAPHE NUCLEUS AND HIPPOCAMPUS: A MICRODIALYSIS STUDY

Abstract number : 2.046
Submission category :
Year : 2004
Submission ID : 4569
Source : www.aesnet.org
Presentation date : 12/2/2004 12:00:00 AM
Published date : Dec 1, 2004, 06:00 AM

Authors :
1,4Liangwei Chu, 4Luc Zimmer, 1,4Sandrine Bouvard, 1,3Gustavo Polo, and 1,2,4Philippe Ryvlin

Vagus nerve stimulation (VNS) is a treatment for patients with medically refractory epilepsy. Although its efficacy has been well established, the mechanism of action of VNS remains unknown. As an inhibitory neurotransmitter, serotonin displayed its antiepileptic effect on various animal models of epilepsy. It was thought to be involved in VNS[rsquo] antiepileptic mechanism after VNS[rsquo] antidepressant effect was demonstrated. From the point of view of nervous anatomy, there is a close relationship between vagus nerve, nucleus of the solitary tract (NTS) and raphe nucleus, which is the major source of serotoninergic neurons. Based on this knowledge, we hypothesized that VNS could evoke a serotonin release in the dorsal raphe nucleus and hippocampus. Male Sprague Dawley rats were implanted with a cuff electrode on the left cervical vagus nerve. The next day, 2 microdialysis probes were implanted respectively in the dorsal raphe nucleus and hippocampus. 2 hours after the probes implantation, dialysates were sampled every 20 minutes. After the establishment of baseline, VNS was given to the rats in stimulation groups (n=6) for 20 minutes while the controls (n=5) received a sham stimulation. Dialysates continued to be collected after VNS for 3 hours and then analysed by HPLC (High Performance Liquid Chromatography) and electrochemical detection. Relative concentration of 5-HT was calculated as the ratio of the measured value at any time point to that of the baseline data. No change in 5-HT concentration was detected during the 20 min stimulation period. Conversely, the extracellular serotonin concentration decreased significantly during the following 2 hours in the dorsal raphe nucleus of stimulated animals (37% [plusmn] 13%) as compared to controls (79% [plusmn] 27%) (p[lt]0,01). This effect was not observed in the hippocampus. The decrease of extracellular serotonin concentration in the dorsal raphe nucleus observed in this study suggests that the synthesis, release or reuptake of serotonin could be modified by an acute VNS, although our results are contrary to our primary hypothesis. (Supported by Cyberonics, Inc)