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

Brain Stimulation
Anne M LandauDoris J Doudet

Abstract

Vagal nerve stimulation (VNS) emerged as an anti-epileptic therapy, and more recently as a potential antidepressant intervention. 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 α2 adrenoceptor binding. Using positron emission tomography (PET), we measured changes in noradrenaline receptor binding associated with acute VNS stimulation in six anesthetized Göttingen minipigs. We used the selective α2 adrenoceptor antagonist [11C]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 (VND), to calculate binding potentials for selected brain regions of each animal. VNS treatment marked...Continue Reading

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Citations

Jan 30, 2016·Brain Stimulation·Daniel R HulseyMichael P Kilgard
May 17, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Anne M LandauDoris J Doudet
Aug 3, 2018·Expert Review of Medical Devices·Ann MertensKristl Vonck
Sep 5, 2019·Frontiers in Neuroscience·Khalid B MirzaChristofer Toumazou
Jun 7, 2017·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Flavia R Carreno, Alan Frazer
Oct 26, 2018·Scientific Reports·Thea P LillethorupAnne M Landau
Jan 30, 2020·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Anne M LandauMichael Winterdahl
Jul 18, 2020·Nature Communications·Monja P NeuserNils B Kroemer
Jun 10, 2020·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Majken Borup ThomsenAnne M Landau
Apr 25, 2021·Neuroscience and Biobehavioral Reviews·Yue WangAilin Luo

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