title: Acute Vagal Nerve Stimulation Lowers α2 Adrenoceptor Availability: Possible Mechanism of Therapeutic Action.
abstract: BACKGROUND
  Vagal nerve stimulation (VNS) emerged as an anti-epileptic therapy, and more recently as a potential antidepressant intervention.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  The result is consistent with release of noradrenaline by antidepressant therapy, implying a possible explanation for the antidepressant effect of VNS.
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University and Hospital, Nørrebrogade 44, Building 10, Aarhus 8000, Denmark; Center of Functionally Integrative Neuroscience/MINDLab, Aarhus University, Nørrebrogade 44, Building 10, Aarhus 8000, Denmark. Electronic address: alandau@clin.au.dk.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Landau
authors.affiliation: Department of Neurosurgery, Aarhus University Hospital, Nørrebrogade 44, Building 10, Aarhus 8000, Denmark.
authors.forename: Suzan
authors.initials: S
authors.lastname: Dyve
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University and Hospital, Nørrebrogade 44, Building 10, Aarhus 8000, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Jakobsen
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University and Hospital, Nørrebrogade 44, Building 10, Aarhus 8000, Denmark.
authors.forename: Aage K O
authors.initials: AK
authors.lastname: Alstrup
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University and Hospital, Nørrebrogade 44, Building 10, Aarhus 8000, Denmark; Department of Neuroscience and Pharmacology, Copenhagen University, 3 Blegdamsvej, Copenhagen 2200N, Denmark.
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University and Hospital, Nørrebrogade 44, Building 10, Aarhus 8000, Denmark; Division of Neurology, Department of Medicine, University of British Columbia, 2221 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada.
authors.forename: Doris J
authors.initials: DJ
authors.lastname: Doudet
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D059907:Functional Neuroimaging; D007700:Kinetics; D008032:Limbic System / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013552:Swine; D013556:Swine, Miniature; D013787:Thalamic Nuclei / Q000000981:diagnostic imaging / Q000378:metabolism*; D055536:Vagus Nerve Stimulation; D015016:Yohimbine / Q000378:metabolism
chemical_list: D002250:Carbon Radioisotopes; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine
keywords: Brain stimulation; Minipig; Noradrenaline; Positron emission tomography; Vagal nerve stimulation; Yohimbine