Abstracts

Rationale: Vagus Nerve Stimulation (VNS) is a treatment alternative for drug resistant epilepsy and depression. VNS has been the subject of numerous preclinical investigations in the search for underlying therapeutic mechanisms, many of which have been conducted in rats. In our recent studies, however, we found changes in hippocampal physiology during VNS that resemble those observed during brain cooling. Methods: Healthy male rats were implanted with an electrode around the left vagus nerve, a depth electrode in the right hippocampus for EEG and a guide cannula compatible with thermocouple probe in the left hippocampus for intracranial temperature registration. Follow recovery, effects of VNS (18 seconds on/7 seconds off, 1mA, 250 s, 30 Hz) on hippocampal EEG and intracranial temperature were studied in freely moving rats. Effects of VNS on rectal temperature were assessed in separate experimental sessions. In addition, peripheral tail vasomotor response was assessed during VNS with an infrared thermographic camera. Further the locus coeruleus noradrenergic system was lesioned with the selective noradrenergic neurotoxin DSP-4. Results: VNS was produced a robust decrease in both brain (-2.8 0.24C) and rectal temperature (-2.7 0.60 C). Changes in temperature were associated with a decrease in theta peak frequency and a general decrease in hippocampal EEG power. VNS was further found to induce peripheral vasodilation. Lesioning the locus coeruleus noradrenergic system did not attenuate hypothermic effects of VNS. Conclusions: VNS decreases brain and rectal temperature in rats, which probably is the result of heat release induced by peripheral vasodilation. Profound changes in temperature, as found in the present study, has profound influence on general physiology and thus probably on the outcome of several previous VNS studies in rats. Funding: Robrecht Raedt received funding from the Special Research Grant of Ghent University to perform this research