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Increased noradrenaline and adrenaline in plasma and urine have been documented in PTSD. Dopamine-\u03b2-hydroxylase (DBH) catalyzes the conversion of dopamine to noradrenaline and consequently, DBH inhibition reduces catecholamines. Our aim was to evaluate if nepicastat treatment decreases PTSD signs in an animal model. Wild-type (129x1\/SvJ) female mice were submitted to PTSD induction protocol. DBH-inhibitor nepicastat (30 mg\/kg) or vehicle (0.2% HPMC) were administered once daily since day 0 until day 7 or 12. The percentage of freezing was calculated on days 0, 1, 2, and 7, and behavioral tests were performed. Quantification of nepicastat in plasma and DBH activity in the adrenal gland was evaluated. Catecholamines were quantified by HPLC with electrochemical detection. mRNA expression of<jats:italic>Npas4<\/jats:italic>and<jats:italic>Bdnf<\/jats:italic>in hippocampus was evaluated by qPCR.Mice in the PTSD-group and treated with nepicastat showed a decrease in freezing, and an increase in the time spent and entries in open arms in elevated plus maze test. In mice treated with nepicastat, adrenal gland DBH activity was decreased, and catecholamines were also decreased in plasma and tissues. On day 7, in mice treated with nepicastat, there was an increase of<jats:italic>Npas4<\/jats:italic>and<jats:italic>Bdnf<\/jats:italic>mRNA expression in the hippocampus.In conclusion, DBH inhibitor nepicastat has an effect consistent with a decrease in the persistence of traumatic memories and anxiety-like behavior in this PTSD mice model. The disruption of traumatic memories through interference with the formation, consolidation, retrieval, and\/or expression processes may be important to decrease PTSD symptoms and signs. The increase in<jats:italic>Npas4<\/jats:italic>and<jats:italic>Bdnf<\/jats:italic>mRNA expression in the hippocampus may be important to develop a weaker traumatic contextual memory after nepicastat treatment.<\/jats:p>","DOI":"10.3389\/fnmol.2021.745219","type":"journal-article","created":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T00:44:53Z","timestamp":1632530693000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Treatment With Nepicastat Decreases Contextual Traumatic Memories Persistence in Post-traumatic Stress Disorder"],"prefix":"10.3389","volume":"14","author":[{"given":"Raquel","family":"Martinho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Correia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela","family":"Seixas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soraia","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Serr\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Fernandes-Lopes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Moreira-Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.tins.2004.11.001","article-title":"Mechanisms of memory stabilization: are consolidation and reconsolidation similar or distinct processes?","volume":"28","author":"Alberini","year":"2005","journal-title":"Trends Neurosci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1007\/s00213-016-4254-5","article-title":"Epinephrine increases contextual learning through activation of peripheral \u03b22-adrenoceptors","volume":"233","author":"Alves","year":"2016","journal-title":"Psychopharmacology"},{"key":"B3","volume-title":"Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition: (DSM-5).","year":"2013"},{"key":"B4","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1155\/NP.2000.133","article-title":"Through the looking glass: differential noradenergic modulation of prefrontal cortical function","volume":"7","author":"Arnsten","year":"2000","journal-title":"Neural Plast."},{"key":"B5","doi-asserted-by":"publisher","first-page":"i6","DOI":"10.1093\/cercor\/bhm033","article-title":"Catecholamine and second messenger influences on prefrontal cortical networks of \u201crepresentational knowledge\u201d: a rational bridge between genetics and the symptoms of mental illness","volume":"17","author":"Arnsten","year":"2007","journal-title":"Cereb. 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