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A non\u2010invasive form of VNS is transcutaneous auricular VNS (taVNS). Combining animal models and positron emission tomography (PET) may lead to a better understanding of the elusive mechanisms of taVNS. We evaluated the acute effect of electrical stimulation of the left vagus nerve via the ear on brain synaptic vesicle glycoprotein 2A (SV2A) as a measure of presynaptic density and glucose metabolism in na\u00efve rats. Female Sprague\u2013Dawley rats were imaged with [<jats:sup>11<\/jats:sup>C]UCB\u2010J (<jats:italic>n<\/jats:italic>\u2009=\u200911) or [<jats:sup>18<\/jats:sup>F]fluorodeoxyglucose ([<jats:sup>18<\/jats:sup>F]FDG) PET (<jats:italic>n<\/jats:italic>\u2009=\u200913) on two separate days, (1) at baseline, and (2) after acute unilateral left taVNS or sham stimulation (30\u2009min). We calculated the regional volume of distribution (V<jats:sub>T<\/jats:sub>) for [<jats:sup>11<\/jats:sup>C]UCB\u2010J and standard uptake values (SUV) for [<jats:sup>18<\/jats:sup>F]FDG. We observed regional reductions of [<jats:sup>11<\/jats:sup>C]UCB\u2010J binding in response to taVNS ranging from 36% to 59%. The changes in taVNS compared to baseline were significantly larger than those induced by sham stimulation. The differences were observed bilaterally in the frontal cortex, striatum, and midbrain. The [<jats:sup>18<\/jats:sup>F]FDG PET uptake remained unchanged following acute taVNS or sham stimulation compared to baseline values. This proof\u2010of\u2010concept study shows for the first time that acute taVNS for 30\u2009min can modulate in\u00a0vivo synaptic SV2A density in cortical and subcortical regions of healthy rats. Preclinical disease models and PET ligands of different targets can be a powerful combination to assess the therapeutic potential of taVNS.<\/jats:p>","DOI":"10.1111\/psyp.14709","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T02:24:00Z","timestamp":1729477440000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Acute transcutaneous auricular vagus nerve stimulation modulates presynaptic <scp>SV2A<\/scp> density in healthy rat brain: An in\u00a0vivo <scp>microPET<\/scp> study"],"prefix":"10.1111","volume":"62","author":[{"given":"Karina H.","family":"Binda","sequence":"first","affiliation":[{"name":"Translational Neuropsychiatry Unit, Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline C.","family":"Real","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette T.","family":"Simonsen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebbe K.","family":"Grove","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Bender","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Gjedde","sequence":"additional","affiliation":[{"name":"Translational Neuropsychiatry Unit, Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Department of Neuroscience University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Neurology and Neurosurgery McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Institute of Translational and Clinical Research, University of Newcastle upon Tyne  Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7371-8713","authenticated-orcid":false,"given":"Anne M.","family":"Landau","sequence":"additional","affiliation":[{"name":"Translational Neuropsychiatry Unit, Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1957.sp005703"},{"key":"e_1_2_11_3_1","first-page":"793","volume-title":"The cranial nerves. 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