Acute Vagal Nerve Stimulation Lowers α2 Adrenoceptor Availability: Possible Mechanism of Therapeutic Action
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
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 journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
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 K. O.
AU - Gjedde, Albert
AU - Doudet, Doris J.
PY - 2015
Y1 - 2015
N2 - BackgroundVagal nerve stimulation (VNS) emerged as an anti-epileptic therapy, and more recently as a potential antidepressant intervention.Objective/hypothesisWe 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.MethodsUsing 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.ResultsVNS treatment markedly reduced the binding potential of yohimbine in limbic, thalamic and cortical brain regions, in inverse correlation with the baseline binding potential.ConclusionThe result is consistent with release of noradrenaline by antidepressant therapy, implying a possible explanation for the antidepressant effect of VNS.
AB - BackgroundVagal nerve stimulation (VNS) emerged as an anti-epileptic therapy, and more recently as a potential antidepressant intervention.Objective/hypothesisWe 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.MethodsUsing 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.ResultsVNS treatment markedly reduced the binding potential of yohimbine in limbic, thalamic and cortical brain regions, in inverse correlation with the baseline binding potential.ConclusionThe result is consistent with release of noradrenaline by antidepressant therapy, implying a possible explanation for the antidepressant effect of VNS.
KW - Brain stimulation
KW - Minipig
KW - Noradrenaline
KW - Positron emission tomography
KW - Vagal nerve stimulation
KW - Yohimbine
U2 - 10.1016/j.brs.2015.02.003
DO - 10.1016/j.brs.2015.02.003
M3 - Journal article
C2 - 25758422
VL - 8
SP - 702
EP - 707
JO - Brain Stimulation
JF - Brain Stimulation
SN - 1935-861X
IS - 4
ER -
ID: 160922358