Acute vagal nerve stimulation lowers α2 adrenoceptor availability

Possible mechanism of therapeutic action

Anne M. Landau, Suzan Dyve, Steen Jakobsen, Aage K O Alstrup, Albert Gjedde, Doris J. Doudet

Research output: Contribution to journalArticle

Abstract

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 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. Conclusion The result is consistent with release of noradrenaline by antidepressant therapy, implying a possible explanation for the antidepressant effect of VNS.

Original languageEnglish (US)
Pages (from-to)702-707
Number of pages6
JournalBrain Stimulation
Volume8
Issue number4
DOIs
StatePublished - 2015
Externally publishedYes

Fingerprint

Vagus Nerve Stimulation
Adrenergic Receptors
Antidepressive Agents
Miniature Swine
Yohimbine
Positron-Emission Tomography
Therapeutics
Norepinephrine
Ligands
Brain
Synaptic Transmission
Electrodes
Biomarkers

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Biophysics
  • Medicine(all)

Cite this

Landau, A. M., Dyve, S., Jakobsen, S., Alstrup, A. K. O., Gjedde, A., & Doudet, D. J. (2015). Acute vagal nerve stimulation lowers α2 adrenoceptor availability: Possible mechanism of therapeutic action. Brain Stimulation, 8(4), 702-707. https://doi.org/10.1016/j.brs.2015.02.003

Acute vagal nerve stimulation lowers α2 adrenoceptor availability : Possible mechanism of therapeutic action. / Landau, Anne M.; Dyve, Suzan; Jakobsen, Steen; Alstrup, Aage K O; Gjedde, Albert; Doudet, Doris J.

In: Brain Stimulation, Vol. 8, No. 4, 2015, p. 702-707.

Research output: Contribution to journalArticle

Landau, AM, Dyve, S, Jakobsen, S, Alstrup, AKO, Gjedde, A & Doudet, DJ 2015, 'Acute vagal nerve stimulation lowers α2 adrenoceptor availability: Possible mechanism of therapeutic action', Brain Stimulation, vol. 8, no. 4, pp. 702-707. https://doi.org/10.1016/j.brs.2015.02.003
Landau, Anne M. ; Dyve, Suzan ; Jakobsen, Steen ; Alstrup, Aage K O ; Gjedde, Albert ; Doudet, Doris J. / Acute vagal nerve stimulation lowers α2 adrenoceptor availability : Possible mechanism of therapeutic action. In: Brain Stimulation. 2015 ; Vol. 8, No. 4. pp. 702-707.
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