{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T05:55:25Z","timestamp":1793858125399,"version":"4.6.1"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero Dell'Universit\u00e0 e Della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Post-traumatic stress disorder (PTSD) is a chronic psychiatric condition characterized by persistent cognitive and affective disturbances following exposure to severe trauma. In rodents, prolonged post-weaning social isolation is a well-established model of PTSD-like symptomatology. In this study, we investigated the behavioral effects of chronic cannabidiol (CBD) administration\u2014either alone or in combination with two natural antioxidants, resveratrol (RES) and alpha-lipoic acid (ALA)in socially isolated mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male CD1 mice (n = 8) were isolated in individual cages from postnatal day 21 (PN21) and maintained in isolation for 30 days. They were then treated with CBD (2.5, 5, and 10\u00a0mg\/kg), resveratrol (RES, 20\u00a0mg\/kg), or alpha-lipoic acid (ALA, 10\u00a0mg\/kg) for 15 days following social isolation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>While low-dose CBD (2.5\u00a0mg\/kg) alone was ineffective, its combination with either RES or ALA restored the latency to the first attack and significantly reduced aggressive behavior, comparable to high-dose CBD (10\u00a0mg\/kg). Similarly, combined treatments with RES or ALA markedly reduced immobility time in the tail suspension test, indicating antidepressant-like effects. In contrast, no significant anxiolytic effect was observed with the combinations in the hole-board test, suggesting a limited action on anxiety-like behavior.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings suggest that co-administration of CBD with RES or ALA exerts synergistic antidepressants and anti-aggressive effects in a PTSD-like model, potentially allowing for dose reduction of CBD. Further studies are warranted to explore the underlying molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1676421","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:39:48Z","timestamp":1761719988000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The neuroprotective effect of cannabidiol is enhanced by resveratrol and alpha-lipoic acid in social isolation"],"prefix":"10.3389","volume":"16","author":[{"given":"Federica","family":"Ricciardi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Maria","family":"Morace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Limongelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Iannotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Boccella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antimo","family":"Fusco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roozbe","family":"Bonsale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Perrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosmara","family":"Infantino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Di Martino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Consalvo","family":"Mattia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Gargano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Consiglia","family":"Trotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enza","family":"Palazzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabatino","family":"Maione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Guida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livio","family":"Luongo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Belardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1007\/s00394-016-1245-6","article-title":"Benefits of l-alanine or l-arginine supplementation against adiposity and glucose intolerance in monosodium glutamate-induced obesity","volume":"56","author":"Araujo","year":"2017","journal-title":"Eur. 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