{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T09:40:13Z","timestamp":1772271613804,"version":"3.50.1"},"reference-count":22,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fujian Provincial Science and Technology Planning Projects","award":["2024Y0077 and 2024N0022"],"award-info":[{"award-number":["2024Y0077 and 2024N0022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Depression remains a major global health challenge, with a significant proportion of patients failing to respond to conventional antidepressants. This study aimed to evaluate the potential antidepressant effects and toxicological profile of a novel tetrodotoxin (TTX) oral film formulation in a mouse model of chronic unpredictable mild stress (CUMS). Male C57BL\/6J mice were subjected to CUMS and treated daily with TTX oral film at doses of 10, 20, and 40 \u03bcg\/kg, with fluoxetine (18 mg\/kg) serving as a positive control. Behavioral assessments, including sucrose preference test, open field test, forced swimming test, elevated plus maze, and novel object recognition, demonstrated that TTX oral film administration alleviated depression- and anxiety-like behaviors and improved cognitive function. Furthermore, TTX oral film treatment restored hippocampal serotonin levels, which were depleted in CUMS mice, and showed no adverse effects on organ indexes after long-term use. Toxicological evaluation through acute toxicity testing revealed an oral LD50 of 919 \u03bcg\/kg, indicating a substantially improved safety profile compared to pure TTX and a wide therapeutic window. These findings suggest that the TTX oral film possesses significant antidepressant activity with favorable toxicological properties, supporting its potential as a novel and safe treatment for depression.<\/jats:p>","DOI":"10.3390\/md24030094","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T16:57:13Z","timestamp":1772125033000},"page":"94","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tetrodotoxin Oral Film Attenuates Depression in a Chronic Unpredictable Mild Stress Model in Mice"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3327-5767","authenticated-orcid":false,"given":"Jianlin","family":"He","sequence":"first","affiliation":[{"name":"Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"},{"name":"Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Tang","sequence":"additional","affiliation":[{"name":"Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"},{"name":"Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siwen","family":"Niu","sequence":"additional","affiliation":[{"name":"Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"},{"name":"Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingqing","family":"Le","sequence":"additional","affiliation":[{"name":"Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"},{"name":"Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Yu","sequence":"additional","affiliation":[{"name":"Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"},{"name":"Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bihong","family":"Hong","sequence":"additional","affiliation":[{"name":"Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China"},{"name":"Technical Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.amepre.2022.05.014","article-title":"Trends in US depression prevalence from 2015 to 2020: The widening treatment gap","volume":"63","author":"Goodwin","year":"2022","journal-title":"Am. 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