{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:03:00Z","timestamp":1792519380194,"version":"4.5.0"},"reference-count":140,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institute for Health Research","doi-asserted-by":"publisher","award":["201309OG-312343-PT"],"award-info":[{"award-number":["201309OG-312343-PT"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institute for Health Research","doi-asserted-by":"publisher","award":["201803PJT-399980-PT"],"award-info":[{"award-number":["201803PJT-399980-PT"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institute for Health Research","doi-asserted-by":"publisher","award":["RGPIN-2015-04034"],"award-info":[{"award-number":["RGPIN-2015-04034"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Graham Boeckh Foundation","award":["201309OG-312343-PT"],"award-info":[{"award-number":["201309OG-312343-PT"]}]},{"name":"Graham Boeckh Foundation","award":["201803PJT-399980-PT"],"award-info":[{"award-number":["201803PJT-399980-PT"]}]},{"name":"Graham Boeckh Foundation","award":["RGPIN-2015-04034"],"award-info":[{"award-number":["RGPIN-2015-04034"]}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council","doi-asserted-by":"publisher","award":["201309OG-312343-PT"],"award-info":[{"award-number":["201309OG-312343-PT"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council","doi-asserted-by":"publisher","award":["201803PJT-399980-PT"],"award-info":[{"award-number":["201803PJT-399980-PT"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council","doi-asserted-by":"publisher","award":["RGPIN-2015-04034"],"award-info":[{"award-number":["RGPIN-2015-04034"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Noradrenaline (NE) plays an integral role in shaping behavioral outcomes including anxiety\/depression, fear, learning and memory, attention and shifting behavior, sleep-wake state, pain, and addiction. However, it is unclear whether dysregulation of NE release is a cause or a consequence of maladaptive orientations of these behaviors, many of which associated with psychiatric disorders. To address this question, we used a unique genetic model in which the brain-specific vesicular monoamine transporter-2 (VMAT2) gene expression was removed in NE-positive neurons disabling NE release in the entire brain. We engineered VMAT2 gene splicing and NE depletion by crossing floxed VMAT2 mice with mice expressing the Cre-recombinase under the dopamine \u03b2-hydroxylase (DBH) gene promotor. In this study, we performed a comprehensive behavioral and transcriptomic characterization of the VMAT2DBHcre KO mice to evaluate the role of central NE in behavioral modulations. We demonstrated that NE depletion induces anxiolytic and antidepressant-like effects, improves contextual fear memory, alters shifting behavior, decreases the locomotor response to amphetamine, and induces deeper sleep during the non-rapid eye movement (NREM) phase. In contrast, NE depletion did not affect spatial learning and memory, working memory, response to cocaine, and the architecture of the sleep-wake cycle. Finally, we used this model to identify genes that could be up- or down-regulated in the absence of NE release. We found an up-regulation of the synaptic vesicle glycoprotein 2c (SV2c) gene expression in several brain regions, including the locus coeruleus (LC), and were able to validate this up-regulation as a marker of vulnerability to chronic social defeat. The NE system is a complex and challenging system involved in many behavioral orientations given it brain wide distribution. In our study, we unraveled specific role of NE neurotransmission in multiple behavior and link it to molecular underpinning, opening future direction to understand NE role in health and disease.<\/jats:p>","DOI":"10.3390\/biom13030511","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T04:35:41Z","timestamp":1678682141000},"page":"511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Behavioral and Transcriptomic Changes Following Brain-Specific Loss of Noradrenergic Transmission"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0698-4237","authenticated-orcid":false,"given":"Elsa","family":"Isingrini","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Douglas Hospital, Mc Gill University, Montreal, QC H4H 1R3, Canada"},{"name":"Facult\u00e9 des Sciences Fondamentales et Biom\u00e9dicales, Universit\u00e9 Paris Cit\u00e9, INCC UMR 8002, CNRS, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00e9","family":"Guinaudie","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Douglas Hospital, Mc Gill University, Montreal, QC H4H 1R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4506-4414","authenticated-orcid":false,"given":"L\u00e9a","family":"Perret","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Douglas Hospital, Mc Gill University, Montreal, QC H4H 1R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4651-8529","authenticated-orcid":false,"given":"Elisa","family":"Guma","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Douglas Hospital, Mc Gill University, Montreal, QC H4H 1R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Gorgievski","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Douglas Hospital, Mc Gill University, Montreal, QC H4H 1R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6999-8364","authenticated-orcid":false,"given":"Ian D.","family":"Blum","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Douglas Hospital, Mc Gill University, Montreal, QC H4H 1R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Colby-Milley","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Douglas Hospital, Mc Gill University, Montreal, QC H4H 1R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9719-1963","authenticated-orcid":false,"given":"Maryia","family":"Bairachnaya","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Douglas Hospital, Mc Gill University, Montreal, QC H4H 1R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8679-5718","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Mella","sequence":"additional","affiliation":[{"name":"Cytometry and Biomarkers Platform, Unit of Technology and Service, Institut Pasteur, Universit\u00e9 de Paris, F-75015 Paris, France"},{"name":"Bioinformatics and Biostatistics Hub Platform, Institut Pasteur, Universit\u00e9 de Paris, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2531-5175","authenticated-orcid":false,"given":"Antoine","family":"Adamantidis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Douglas Hospital, Mc Gill University, Montreal, QC H4H 1R3, Canada"},{"name":"Zentrum f\u00fcr Experimentelle Neurologie, Department of Neurology, Inselspital University Hospital Bern, 3010 Bern, Switzerland"},{"name":"Department of Biomedical Research, University of Bern, 3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Florian","family":"Storch","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Douglas Hospital, Mc Gill University, Montreal, QC H4H 1R3, 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