Steen Jakobsen

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

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Acute Vagal Nerve Stimulation Lowers α2 Adrenoceptor Availability : Possible Mechanism of Therapeutic Action. / Landau, Anne M.; Dyve, Suzan; Jakobsen, Steen; Alstrup, Aage Kristian Olsen; Gjedde, Albert; Doudet, Doris.

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

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@article{32e5828548ae4123a85a3da9230d5248,
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/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 G{\"o}ttingen 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.",
author = "Landau, {Anne M.} and Suzan Dyve and Steen Jakobsen and Alstrup, {Aage Kristian Olsen} and Albert Gjedde and Doris Doudet",
year = "2015",
doi = "10.1016/j.brs.2015.02.003",
language = "English",
volume = "8",
pages = "702--707",
journal = "Brain Stimulation",
issn = "1935-861X",
publisher = "Elsevier Inc",
number = "4",

}

RIS

TY - JOUR

T1 - Acute Vagal Nerve Stimulation Lowers α2 Adrenoceptor Availability

T2 - Possible Mechanism of Therapeutic Action

AU - Landau, Anne M.

AU - Dyve, Suzan

AU - Jakobsen, Steen

AU - Alstrup, Aage Kristian Olsen

AU - Gjedde, Albert

AU - Doudet, Doris

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1016/j.brs.2015.02.003

DO - 10.1016/j.brs.2015.02.003

M3 - Journal article

VL - 8

SP - 702

EP - 707

JO - Brain Stimulation

JF - Brain Stimulation

SN - 1935-861X

IS - 4

ER -