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Behavioral assessments, including the tail suspension test (TST), forced swimming test (FST), and sucrose splash test (SST), were conducted on days 0, 5, 10, and 15. Molecular docking and pathway analyses were performed to provide insight into its possible mechanism of action.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CRS exposure successfully induced depressive-like behavior, characterized by prolonged immobility in the TST and FST and diminished grooming activity in the SST. Administration of aminophylline attenuated these behavioral deficits, reducing immobility time and increasing grooming time in a dose-dependent manner. Molecular docking analysis demonstrated favorable binding of aminophylline to phosphodiesterase 3, phosphodiesterase 4, and the serotonin transporter, targets associated with antidepressant activity. Pathway analysis revealed upregulation of PPAR signaling, calcium signaling, and the synaptic vesicle cycle, while downregulating the glutamatergic synapse pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The study provides the first evidence of the antidepressant activity of aminophylline in a validated model of depression, prompting further clinical investigation into its therapeutic potential. Moreover, molecular and biochemical analyses are warranted to validate its precise mechanism of action.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s43440-026-00851-9","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T07:24:54Z","timestamp":1775546694000},"page":"748-761","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Potential antidepressant properties of aminophylline in male mice exposed to chronic restraint stress"],"prefix":"10.1007","volume":"78","author":[{"given":"Florence Ingred","family":"Samante","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine Gale","family":"Galangue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie Chenn","family":"Avelino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoneitte Joy","family":"Beltran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Rapada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eldan Greg","family":"Pabia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niel Andrew","family":"Bustamante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrislean Jun","family":"Botanas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred Lawrence","family":"Samante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina Joy","family":"Bormate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raly James Perez","family":"Custodio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"851_CR1","unstructured":"Association AP. 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Trends Neurosci. 2012;35(1):47\u201356.","journal-title":"Trends Neurosci"}],"container-title":["Pharmacological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43440-026-00851-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43440-026-00851-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43440-026-00851-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T09:02:46Z","timestamp":1781686966000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43440-026-00851-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":60,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["851"],"URL":"https:\/\/doi.org\/10.1007\/s43440-026-00851-9","relation":{},"ISSN":["1734-1140","2299-5684"],"issn-type":[{"value":"1734-1140","type":"print"},{"value":"2299-5684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]},"assertion":[{"value":"8 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 March 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experimental procedures were formally reviewed and approved by the Bureau of Animal Industry (BAI) of the Philippines under Republic Act No. 8485 (Animal Welfare Act) on January 26, 2024. Although no Institutional Animal Care and Use Committee (IACUC) is available at the animal facility of the Department of Health Schistosomiasis Research and Training Center, the approval granted by the BAI authorizes the conduct of experiments at this facility under the guidance and close supervision of veterinarians from BAI Region VIII. Both the Department of Health Schistosomiasis Research and Training Center and the Bureau of Animal Industry of the Philippines are government institutions that work collaboratively to ensure that all experimental procedures are conducted ethically and in full compliance with national regulations. Furthermore, all experiments were carried out in strict accordance with the ARRIVE Guidelines, NIH regulations, and the principles of Replacement, Reduction, and Refinement (3Rs), with every effort made to maintain the highest standards of animal welfare and to minimize suffering throughout the study. The official approval letter is provided as a supplementary file.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Animal ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}