{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T07:27:31Z","timestamp":1774510051589,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DFG FOR2591","award":["TA2072\/1-1"],"award-info":[{"award-number":["TA2072\/1-1"]}]},{"name":"DFG FOR2591","award":["GA 427\/12-3"],"award-info":[{"award-number":["GA 427\/12-3"]}]},{"name":"DFG FOR2591","award":["MA 11040\/2-3"],"award-info":[{"award-number":["MA 11040\/2-3"]}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"crossref","award":["01EE2304A"],"award-info":[{"award-number":["01EE2304A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Union NextGenerationEU"},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Pharmacological antidepressant treatments alter the molecular and functional reactivity of stress-sensitive neural networks. However, how classical versus rapid-acting antidepressants differentially modulate acute stress-induced transcriptional responses across brain regions remains unclear. Here, we compared imipramine and ketamine in mice exposed to acute swim stress, assessing transcriptional adaptations across the frontal cortex, hippocampus, and striatum. Swim stress induced significant widespread activation of cFOS, which led to drug-specific modulations: imipramine primarily significantly dampened cortical and striatal cFOS expression, whereas ketamine preserved stress-evoked neuronal activation. In contrast, hippocampal activation was significantly robust but largely unaffected, indicating that acute antidepressant drug effects during stress coping preferentially target cortical and striatal plasticity mechanisms. In contrast, BDNF expression was altered only within the striatal region, where imipramine attenuated the stress-related increase in BDNF expression. Statistical analysis of behavioral outcomes during the swim stress confirmed a shared facilitation of active coping, yet these similar outcomes emerged from distinct molecular programs. Together, the data demonstrate that the treatment effects of the two substances diverge mechanistically, revealing cortical and striatal transcriptional signatures of classical versus rapid-acting antidepressant action. While these findings suggest potential translational relevance for understanding distinct mechanisms, further studies in humans are required to validate these signatures and their clinical implications.<\/jats:p>","DOI":"10.3390\/biom16040484","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T08:02:49Z","timestamp":1774339369000},"page":"484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct Molecular Responses to Ketamine and Imipramine in Cortical and Striatal Regions Following Acute Swim Stress"],"prefix":"10.3390","volume":"16","author":[{"given":"Veronica","family":"Begni","sequence":"first","affiliation":[{"name":"Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6869-5337","authenticated-orcid":false,"given":"Floriana","family":"De Cillis","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natascha","family":"Pfeiffer","sequence":"additional","affiliation":[{"name":"RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9062-4065","authenticated-orcid":false,"given":"Steven Roger","family":"Talbot","sequence":"additional","affiliation":[{"name":"Institute for Laboratory Animal Science, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Gass","sequence":"additional","affiliation":[{"name":"RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany"},{"name":"German Center for Mental Health (DZPG), Partner Site Mannheim, Heidelberg, Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9963-848X","authenticated-orcid":false,"given":"Annamaria","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"},{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1699-5060","authenticated-orcid":false,"given":"Marco Andrea","family":"Riva","sequence":"additional","affiliation":[{"name":"Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"},{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8082-6798","authenticated-orcid":false,"given":"Anne Stephanie","family":"Mallien","sequence":"additional","affiliation":[{"name":"RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41392-024-01738-y","article-title":"Major Depressive Disorder: Hypothesis, Mechanism, Prevention and Treatment","volume":"9","author":"Cui","year":"2024","journal-title":"Signal Transduct. 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