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This study evaluated and compared the effect of the deacetyl derivative in a chronic restrain model of depression. In the first phase of the study, the synergistic potential of dXA was evaluated using the mouse tail suspension test (TST) and forced swim test (FST). In the second phase, mice were subjected to chronic restraint stress for 42\u00a0days, starting from day 0, in ventilated tubes (0800\u20131400\u00a0h). On day 42, stress-na\u00efve and stressed mice were assessed using both the FST and TST to identify the more sensitive behavioural assay for subsequent evaluation of treatment effects. Stressed mice were then administered fluoxetine, XA, dXA, vehicle for 72\u00a0h or single acute dosing of combinations of fluoxetine with XA or dXA, followed by repeat behavioural testing 90\u00a0min after the last dose of either a single acute or a chronic dosing regimen. The interaction index (\n                    <jats:italic>\u03b3<\/jats:italic>\n                    ), together with the significantly lower ED\n                    <jats:sub>50mix<\/jats:sub>\n                    compared to the ED\n                    <jats:sub>50add<\/jats:sub>\n                    , for the dXA combinations, with fluoxetine, sertraline, imipramine and ketamine is indicative of synergistic effect. An 8-hourly dosing, for 72\u00a0h of XA (100\u00a0mg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) and dXA (100\u00a0mg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) in the acute models did not reverse the behavioural traits of chronic restrain. However, fluoxetine (30\u00a0mg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), given 12 hourly for 72\u00a0h, and the acute administration of combinations of fluoxetine (100\u00a0mg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) and dXA (100\u00a0mg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) significantly reversed the duration of immobility. The present study demonstrates that deacetyl xylopic acid (dXA) exerts synergistic antidepressant\u2014like effects with selective antidepressants and augments the antidepressant effects of fluoxetine in a mouse model of chronic restraint stress-induced depression. These findings suggest that dXA may represent a promising adjunctive agent for improving antidepressant efficacy, particularly in stress-related depressive disorders.\n                  <\/jats:p>","DOI":"10.1007\/s00210-026-05501-8","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T17:30:10Z","timestamp":1782840610000},"page":"18015-18028","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deacetyl xylopic acid exhibits synergistic antidepressant-like effects and augments fluoxetine activity in a chronic restraint-induced depression model in mice"],"prefix":"10.1007","volume":"399","author":[{"given":"Charles Kwaku","family":"Benneh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonder Kofi Mensah","family":"Abotsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliu","family":"Moomin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Peter","family":"Biney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Japhat Opoku","family":"Ofosu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustapha Kobina","family":"Abeka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augustine","family":"Tandoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatus Wewura","family":"Adongo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Woode","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"5501_CR1","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1146\/annurev-med-053013-062946","volume":"66","author":"CG Abdallah","year":"2015","unstructured":"Abdallah CG, Sanacora G, Duman RS, Krystal JH (2015) Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics. 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