4.6 Article

Acute Vagal Nerve Stimulation Lowers α2 Adrenoceptor Availability: Possible Mechanism of Therapeutic Action

Journal

BRAIN STIMULATION
Volume 8, Issue 4, Pages 702-707

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.brs.2015.02.003

Keywords

Brain stimulation; Minipig; Noradrenaline; Positron emission tomography; Vagal nerve stimulation; Yohimbine

Funding

  1. Lundbeck Foundation [20082607]

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Background: Vagal nerve stimulation (VNS) emerged as an anti-epileptic therapy, and more recently as a potential antidepressant intervention. Objective/hypothesis: We hypothesized that salutary effects of VNS are mediated, at least in part, by augmentation of the inhibitory effects of cortical monoaminergic neurotransmission at appropriate receptors, specifically adrenoceptors. Our objective was to measure the effect of acute VNS on alpha 2 adrenoceptor binding. Methods: Using positron emission tomography (PET), we measured changes in noradrenaline receptor binding associated with acute VNS stimulation in six anesthetized Gottingen minipigs. We used the selective alpha 2 adrenoceptor antagonist [C-11]yohimbine, previously shown to be sensitive to competition from the receptor's endogenous ligands, as a surrogate marker of monoamine release. PET records were acquired 4-6 weeks after the implant of a VNS electrode in minipigs before and within 30 min of the initiation of 1 mA stimulation. Kinetic analysis with the Logan graphical linearization generated tracer volumes of distribution for each condition. We used an averaged value of the distribution volume of non-displaceable ligand (V-ND), to calculate binding potentials for selected brain regions of each animal. Results: VNS treatment markedly reduced the binding potential of yohimbine in limbic, thalamic and cortical brain regions, in inverse correlation with the baseline binding potential. Conclusion: The result is consistent with release of noradrenaline by antidepressant therapy, implying a possible explanation for the antidepressant effect of VNS. (C) 2015 Elsevier Inc. All rights reserved.

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