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.
Department of Neurosurgery, Aarhus University Hospital, Nørrebrogade 44, Building 10, Aarhus 8000, Denmark.
Brain Stimul. 2015 Jul-Aug;8(4):702-7. doi: 10.1016/j.brs.2015.02.003. Epub 2015 Feb 13.
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.
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 markedly reduced the binding potential of yohimbine in limbic, thalamic and cortical brain regions, in inverse correlation with the baseline binding potential.
The result is consistent with release of noradrenaline by antidepressant therapy, implying a possible explanation for the antidepressant effect of VNS.
迷走神经刺激（VNS）作为一种抗癫痫治疗方法出现，最近又作为一种潜在的抗抑郁干预措施。
目的/假设：我们假设 VNS 的有益效果至少部分是通过增强皮质单胺能神经递质传递在适当受体（特别是肾上腺素能受体）的抑制作用来介导的。我们的目的是测量急性 VNS 对 α2 肾上腺素能受体结合的影响。
使用正电子发射断层扫描（PET），我们测量了在六只麻醉的哥廷根迷你猪中，急性 VNS 刺激对去甲肾上腺素受体结合的影响。我们使用选择性 α2 肾上腺素能受体拮抗剂[11C]育亨宾作为单胺释放的替代标志物，该拮抗剂以前被证明对受体内源性配体的竞争敏感。在迷你猪植入 VNS 电极 4-6 周后，在开始 1 mA 刺激前和刺激后 30 分钟内进行 PET 记录。使用 Logan 图形线性化的动力学分析为每种情况生成示踪剂分布容积。我们使用不可置换配体（VND）的分布容积的平均值来计算每个动物选定脑区的结合潜能。
VNS 治疗显著降低了边缘、丘脑和皮质脑区育亨宾的结合潜能，与基线结合潜能呈负相关。
该结果与抗抑郁治疗中去甲肾上腺素的释放一致，暗示 VNS 抗抑郁作用的可能解释。
