{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:42:39Z","timestamp":1776858159218,"version":"3.51.2"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Histamine H3 receptor-targeting compounds modulate histaminergic tone and downstream monoaminergic\/arousal circuits and have been proposed to exert potential antidepressant-like effects in preclinical models. Methods: We conducted a systematic review and meta-analysis of rodent studies evaluating H3-related interventions on depression-like behavior. We screened 60 records, assessed 12 studies qualitatively (four CORE, eight sensitivity), and included nine studies in random-effects meta-analyses (REML). Primary outcomes were the forced swim test (FST) and tail suspension test (TST); effect sizes were summarized as Hedges\u2019 g (positive values indicate reduced immobility). Results: In the primary ALL analysis, H3-related interventions improved FST outcomes (g = 1.40, 95% CI 0.83\u20131.97; k = 7) and were also associated with improved TST outcomes, albeit with substantial heterogeneity (g = 2.27, 95% CI 0.80\u20133.73; k = 5). CORE-only analyses were directionally consistent but less precise (FST: g = 1.11, 95% CI \u22120.06\u20132.27; k = 3; TST: g = 2.95, 95% CI 0.87\u20135.02; k = 2). Sucrose preference was reported in one study and indicated improvement (g = 1.61, 95% CI 0.29\u20132.92). Conclusions: H3-related interventions show an antidepressant-like signal in rodent FST and TST, with greater heterogeneity for TST, highlighting the need for more standardized and adequately powered preclinical studies.<\/jats:p>","DOI":"10.3390\/life16040698","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:38:14Z","timestamp":1776854294000},"page":"698","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical Evidence for Antidepressant-like Effects of Histamine H3 Receptor Modulation: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"16","author":[{"given":"Ilaria","family":"Pullano","sequence":"first","affiliation":[{"name":"Psychiatric Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5533-5315","authenticated-orcid":false,"given":"Anna Maria","family":"Iazzolino","sequence":"additional","affiliation":[{"name":"Psychiatric Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7373-2665","authenticated-orcid":false,"given":"Stefania","family":"Landi","sequence":"additional","affiliation":[{"name":"Department of Mental Health, Azienda Sanitaria Locale Salerno, 84121 Salerno, Italy"},{"name":"European Biomedical Research Institute of Salerno (EBRIS), 84121 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8301-3401","authenticated-orcid":false,"given":"Annarita","family":"Vignapiano","sequence":"additional","affiliation":[{"name":"Department of Mental Health, Azienda Sanitaria Locale Salerno, 84121 Salerno, Italy"},{"name":"European Biomedical Research Institute of Salerno (EBRIS), 84121 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1854-292X","authenticated-orcid":false,"given":"Francesco","family":"Monaco","sequence":"additional","affiliation":[{"name":"Department of Mental Health, Azienda Sanitaria Locale Salerno, 84121 Salerno, Italy"},{"name":"European Biomedical Research Institute of Salerno (EBRIS), 84121 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7077-3506","authenticated-orcid":false,"suffix":"Jr.","given":"Luca","family":"Steardo","sequence":"additional","affiliation":[{"name":"Psychiatric Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"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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