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BDNF was found to be reduced in patients carrying the human polymorphism in the serotonin transporter promoter region (5-HTTLPR). The serotonin knockout rat (SERT\u2212\/\u2212) is one of the animal models used to investigate the underlying molecular mechanisms of depression in humans. They present decreased BDNF levels, and anxiety- and depression-like behavior. To investigate whether upregulating BDNF would ameliorate the phenotype of SERT\u2212\/\u2212 rats, we overexpressed BDNF locally into the ventral hippocampus and submitted the animals to behavioral testing. The results showed that BDNF overexpression in the vHIP of SERT\u2212\/\u2212 rats promoted higher sucrose preference and sucrose intake; on the first day of the sucrose consumption test it decreased immobility time in the forced swim test and increased the time spent in the center of a novel environment. Furthermore, BDNF overexpression altered social behavior in SERT\u2212\/\u2212 rats, which presented increased passive contact with test partner and decreased solitary behavior. Finally, it promoted decrease in plasma corticosterone levels 60 min after restraint stress. In conclusion, modulation of BDNF IV levels in the vHIP of SERT\u2212\/\u2212 rats led to a positive behavioral outcome placing BDNF upregulation in the vHIP as a potential target to new therapeutic approaches to improve depressive symptoms.<\/jats:p>","DOI":"10.3390\/ijms22095040","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T10:49:51Z","timestamp":1620643791000},"page":"5040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["BDNF Overexpression in the Ventral Hippocampus Promotes Antidepressant- and Anxiolytic-Like Activity in Serotonin Transporter Knockout Rats"],"prefix":"10.3390","volume":"22","author":[{"given":"Danielle M.","family":"Diniz","sequence":"first","affiliation":[{"name":"Centre for Neuroscience, Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Nijmegen Medical Centre, 6525 EN Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7946-2424","authenticated-orcid":false,"given":"Francesca","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, Universita\u2019 degli Studi di Milano, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1837-6519","authenticated-orcid":false,"given":"Paola","family":"Brivio","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, Universita\u2019 degli Studi di Milano, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1699-5060","authenticated-orcid":false,"given":"Marco A.","family":"Riva","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, Universita\u2019 degli Studi di Milano, 20133 Milano, Italy"},{"name":"Biological Psychiatry Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanes","family":"Grandjean","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience, Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Nijmegen Medical Centre, 6525 EN Nijmegen, The Netherlands"},{"name":"Department of Radiology and Nuclear Medicine, Donders Institute, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7621-1010","authenticated-orcid":false,"given":"Judith R.","family":"Homberg","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience, Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Nijmegen Medical Centre, 6525 EN Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3389\/fncel.2019.00066","article-title":"The Impact of Studying Brain Plasticity","volume":"13","year":"2019","journal-title":"Front. 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