{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T16:53:44Z","timestamp":1772643224074,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T00:00:00Z","timestamp":1675641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ISCIII","award":["PI19\/00927"],"award-info":[{"award-number":["PI19\/00927"]}]},{"name":"ISCIII","award":["PID2019-106404RB-I00"],"award-info":[{"award-number":["PID2019-106404RB-I00"]}]},{"name":"ISCIII","award":["RD21\/0012\/0023"],"award-info":[{"award-number":["RD21\/0012\/0023"]}]},{"name":"ISCIII","award":["2018\/0135"],"award-info":[{"award-number":["2018\/0135"]}]},{"name":"Irycis Chromatographic Services and Nervous System Markers Unit","award":["PI19\/00927"],"award-info":[{"award-number":["PI19\/00927"]}]},{"name":"Irycis Chromatographic Services and Nervous System Markers Unit","award":["PID2019-106404RB-I00"],"award-info":[{"award-number":["PID2019-106404RB-I00"]}]},{"name":"Irycis Chromatographic Services and Nervous System Markers Unit","award":["RD21\/0012\/0023"],"award-info":[{"award-number":["RD21\/0012\/0023"]}]},{"name":"Irycis Chromatographic Services and Nervous System Markers Unit","award":["2018\/0135"],"award-info":[{"award-number":["2018\/0135"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Post-stroke mood disorders (PSMD) affect disease prognosis in adults. Adult rodent models underlie the importance of the dopamine (DA) system in PSMD pathophysiology. There are no studies on PSMD after neonatal stroke. We induced neonatal stroke in 7-day-old (P7) rats by temporal left middle cerebral artery occlusion (MCAO). Performance in the tail suspension test (TST) at P14 and the forced swimming test (FST) and open field test (OFT) at P37 were studied to assess PSMD. DA neuron density in the ventral tegmental area, brain DA concentration and DA transporter (DAT) expression as well as D2 receptor (D2R) expression and G-protein functional coupling were also studied. MCAO animals revealed depressive-like symptoms at P14 associated with decreased DA concentration and reduced DA neuron population and DAT expression. At P37, MCAO rats showed hyperactive behavior associated with increased DA concentration, normalization of DA neuron density and decreased DAT expression. MCAO did not modify D2R expression but reduced D2R functionality at P37. MCAO-induced depressive-like symptoms were reversed by the DA reuptake inhibitor GBR-12909. In conclusion, MCAO in newborn rats induced depressive-like symptoms and hyperactive behavior in the medium and long term, respectively, that were associated with alterations in the DA system.<\/jats:p>","DOI":"10.3390\/ijms24043229","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T01:56:48Z","timestamp":1675735008000},"page":"3229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Role of the Dopamine System in Post-Stroke Mood Disorders in Newborn Rats"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9394-4323","authenticated-orcid":false,"given":"Mar\u00eda","family":"Villa","sequence":"first","affiliation":[{"name":"Biomedical Research Foundation, Hospital Cl\u00ednico San Calos-IdISSC, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Mart\u00ednez-Vega","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation, Hospital Cl\u00ednico San Calos-IdISSC, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aar\u00f3n","family":"del Pozo","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation, Hospital Cl\u00ednico San Calos-IdISSC, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Itziar","family":"Muneta-Arrate","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of the Basque Country, UPV\/EHU, 48940 Leioa, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dic en Red de Salud Mental (CIBERSAM), 28007 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"G\u00f3mez-Soria","sequence":"additional","affiliation":[{"name":"Neurobiology Department, IRYCIS, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0477-5757","authenticated-orcid":false,"given":"Carolina","family":"Muguruza","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of the Basque Country, UPV\/EHU, 48940 Leioa, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dic en Red de Salud Mental (CIBERSAM), 28007 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"de Hoz-Rivera","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation, Hospital Cl\u00ednico San Calos-IdISSC, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Romero","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation, Hospital Cl\u00ednico San Calos-IdISSC, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Silva","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation, Hospital Cl\u00ednico San Calos-IdISSC, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-012X","authenticated-orcid":false,"given":"Luis F.","family":"Callado","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of the Basque Country, UPV\/EHU, 48940 Leioa, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dic en Red de Salud Mental (CIBERSAM), 28007 Madrid, Spain"},{"name":"Biocruces-Bizkaia Health Research Institute, 48901 Barakaldo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Jos\u00e9","family":"Casarejos","sequence":"additional","affiliation":[{"name":"Neurobiology Department, IRYCIS, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4405-3545","authenticated-orcid":false,"given":"Jos\u00e9","family":"Mart\u00ednez-Orgado","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation, Hospital Cl\u00ednico San Calos-IdISSC, 28040 Madrid, Spain"},{"name":"Department of Neonatology, Hospital Cl\u00ednico San Calos-IdISSC, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.pediatrneurol.2014.07.031","article-title":"Perinatal Arterial Ischemic Stroke: Presentation, Risk Factors, Evaluation, and Outcome","volume":"51","author":"Lehman","year":"2014","journal-title":"Pediatr. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.siny.2009.07.001","article-title":"Epidemiology and Classification of Perinatal Stroke","volume":"14","author":"Lynch","year":"2009","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1402","DOI":"10.1542\/peds.2011-1148","article-title":"Symptomatic Neonatal Arterial Ischemic Stroke: The International Pediatric Stroke Study","volume":"128","author":"Kirton","year":"2011","journal-title":"Pediatrics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.pediatrneurol.2017.01.016","article-title":"Epidemiology and Outcomes of Arterial Ischemic Stroke in Children: The Canadian Pediatric Ischemic Stroke Registy","volume":"69","author":"deVeber","year":"2017","journal-title":"Pediatr. Neurol."},{"key":"ref_5","first-page":"158","article-title":"Arterial Ischemic Stroke in Children and Young Adults. Contin","volume":"23","author":"Lo","year":"2017","journal-title":"Lifelong Learn. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1080\/09297049.2016.1225708","article-title":"Attention and Executive Functioning Profiles in Children Following Perinatal Arterial Ischemic Stroke","volume":"24","author":"Bosenbark","year":"2018","journal-title":"Child Neuropsychol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"761","DOI":"10.3389\/fpsyt.2018.00761","article-title":"Diversiform Etiologies for Poststroke Depression","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.pharmthera.2017.11.005","article-title":"Post-Stroke Depression: Mechanisms and Pharmacological Treatment","volume":"184","author":"Villa","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"\u00c1lvarez-Garc\u00eda, M., Cuellar-Flores, I., Sierra-Garc\u00eda, P., and Mart\u00ednez-Orgado, J. (2022). Mood Disorders in Children Following Neonatal Hypoxic-Ischemic Encephalopathy. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0263055"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1111\/j.1582-4934.2012.01555.x","article-title":"Post-Stroke Depression: Mechanisms, Translation and Therapy","volume":"16","author":"Loubinoux","year":"2012","journal-title":"J. Cell. Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3892\/etm.2014.1674","article-title":"Monoamine Neurotransmitters and Fibroblast Growth Factor-2 in the Brains of Rats with Post-Stroke Depression","volume":"8","author":"Ji","year":"2014","journal-title":"Exp. Ther. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s42000-018-0007-7","article-title":"Perinatal Hypoxia as a Risk Factor for Psychopathology Later in Life: The Role of Dopamine and Neurotrophins","volume":"17","author":"Giannopoulou","year":"2018","journal-title":"Hormones"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ijdevneu.2007.08.012","article-title":"Recent Trends in Erythropoietin-Mediated Neuroprotection","volume":"26","author":"Mcpherson","year":"2009","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"152","DOI":"10.3389\/fncir.2013.00152","article-title":"Dopamine Signaling in Reward-Related Behaviors","volume":"7","author":"Baik","year":"2013","journal-title":"Front. Neural Circuits"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.neuropharm.2016.12.017","article-title":"Cannabidiol Reduces Brain Damage and Improves Functional Recovery in a Neonatal Rat Model of Arterial Ischemic Stroke","volume":"116","author":"Vargas","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/BF00428203","article-title":"The Tail Suspension Test: A New Method for Screening Antidepressants in Mice","volume":"85","author":"Steru","year":"1985","journal-title":"Psychopharmacology"},{"key":"ref_17","first-page":"327","article-title":"Behavioral Despair in Mice: A Primary Screening Test for Antidepressants","volume":"229","author":"Porsolt","year":"1977","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1007\/s11055-012-9677-9","article-title":"Differences in the Behavior of Impulsive and Self-Controlled Rats in the Open Field and Dark-Light Box Tests","volume":"42","author":"Zaichenko","year":"2012","journal-title":"Neurosci. Behav. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.neuroscience.2015.01.002","article-title":"Characterization of Nociceptive Response to Chemical, Mechanical, and Thermal Stimuli in Adolescent Rats with Neonatal Dopamine Depletion","volume":"289","author":"Ogata","year":"2015","journal-title":"Neuroscience"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2013.04.001","article-title":"Brain Development in Rodents and Humans: Identifying Benchmarks of Maturation and Vulnerability to Injury across Species","volume":"106","author":"Semple","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/mp.2017.16","article-title":"The Dopamine Hypothesis of Bipolar Affective Disorder: The State of the Art and Implications for Treatment","volume":"22","author":"Ashok","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/nrn.2016.57","article-title":"Dysregulation of the Dopamine System in the Pathophysiology of Schizophrenia and Depression","volume":"17","author":"Grace","year":"2016","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Palermo, G., and Ceravolo, R. (2019). Molecular Imaging of the Dopamine Transporter. Cells, 8.","DOI":"10.3390\/cells8080872"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.neuropharm.2008.02.006","article-title":"Direct Enhancement of Hippocampal Dopamine or Serotonin Levels as a Pharmacodynamic Measure of Combined Antidepressant-Anticonvulsant Action","volume":"54","author":"Smolders","year":"2008","journal-title":"Neuropharmacology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/0014-2999(89)90363-4","article-title":"The Dopamine Uptake Inhibitor GBR 12909: Selectivity and Molecular Mechanism of Action","volume":"166","author":"Andersen","year":"1989","journal-title":"Eur. J. Pharmacol."},{"key":"ref_26","first-page":"477","article-title":"Effects of Leptin on Norepinephrine in Acute Ischemic Stroke","volume":"74","author":"Tao","year":"2019","journal-title":"Pharmazie"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1203\/01.PDR.0000169971.64558.5A","article-title":"Erythropoietin Protects Dopaminergic Neurons and Improves Neurobehavioral Outcomes in Juvenile Rats after Neonatal Hypoxia-Ischemia","volume":"58","author":"Demers","year":"2005","journal-title":"Pediatr. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1007\/s43440-021-00305-4","article-title":"Characterization of Dopamine D2 Receptor Coupling to G Proteins in Postmortem Brain of Subjects with Schizophrenia","volume":"73","author":"Egusquiza","year":"2021","journal-title":"Pharmacol. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41380-020-0814-5","article-title":"All Roads Lead to the Motor Cortex: Psychomotor Mechanisms and Their Biochemical Modulation in Psychiatric Disorders","volume":"26","author":"Northoff","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_30","first-page":"776","article-title":"Cannabidiol Administration after Hypoxia-Ischemia to Newborn Rats Reduces Long-Term Brain Injury and Restores Neurobehavioral Function","volume":"63","author":"Pazos","year":"2012","journal-title":"Ropharmacology"},{"key":"ref_31","first-page":"78","article-title":"Intraventricular Hemorrhage Induces Inflammatory Brain Damage with Blood\u2013Brain Barrier Dysfunction in Immature Rats","volume":"93","author":"Villa","year":"2022","journal-title":"Pediatr. Res."},{"key":"ref_32","unstructured":"Paxinos, G., and Watson, C. (1997). The Rat Brain in Stereotaxic Coordinates, Elsevier."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3229\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:26:03Z","timestamp":1760120763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,6]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24043229"],"URL":"https:\/\/doi.org\/10.3390\/ijms24043229","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,6]]}}}