• Annelies Grimonprez, Robrecht Raedt, Jeanelle Portelli, Ine Dauwe, Lars Emil Larsen, Charlotte Bouckaert, Jean Delbeke, Evelien Carrette, Alfred Meurs, Veerle De Herdt, Paul Boon, and Kristl Vonck.
• Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Ghent University, Department of Neurology, Institute for Neuroscience, Ghent, Belgium. Electronic address: Annelies.Grimonprez@UGent.be.
• J Psychiatr Res. 2015 Sep 1; 68: 1-7.

AbstractIt has been shown that vagus nerve stimulation (VNS) has an antidepressant-like effect in the forced swim test. The mechanism of action underlying this effect is incompletely understood, but there is evidence suggesting that the locus coeruleus (LC) may play an important role. In this study, noradrenergic LC neurons were selectively lesioned to test their involvement in the antidepressant-like effect of VNS in the forced swim test. Forced swim test behavior was assessed in rats that were subjected to VNS or sham treatment. In half of the VNS-treated animals, the noradrenergic neurons from the LC were lesioned using the selective neurotoxin DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride], yielding three experimental arms: sham, VNS and DSP-4-VNS (n = 8 per group). Furthermore, the open field test was performed to evaluate locomotor activity. A dopamine-β-hydroxylase immunostaining was performed to confirm lesioning of noradrenergic LC neurons. VNS significantly reduced the percentage of immobility time in the forced swim test compared to sham treatment (median: 56%, interquartile range: 41% vs. median: 75%, interquartile range: 12%). This antidepressant-like effect of VNS could not be demonstrated in the DSP-4-VNS group (median: 79%, interquartile range: 33%). Locomotor activity in the open field test was not different between the three treatment arms. The absence of hippocampal dopamine-β-hydroxylase immunostaining in the DSP-4-treated rats confirmed the lesioning of noradrenergic neurons originating from the brainstem LC. The results of this study demonstrate that the noradrenergic neurons from the LC play an important role in the antidepressant-like effect of VNS.Copyright © 2015 Elsevier Ltd. All rights reserved.

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