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The present research aimed to assess the potential deleterious effects of social isolation on behavioral functions and DAT levels in the medial prefrontal cortex of both sexes of rats. Social isolation was done in two protocols: 25 days (PND45-70) and 50 days (PND20-70). Open field test, hot plate, marble burying test, forced swim test, and western blotting were used. The results showed locomotion, grooming, and climbing were increased in both protocols of social isolation in both sexes. Anxiety-like behavior in the open field test was increased in both protocols of social isolation in males, while in females, only short-term social isolation showed this effect and long-term social isolation decreased it. Sniffing was decreased in both protocols of social isolation in males, while in females, only long-term social isolation increased it. Rearing was decreased in both protocols of social isolation in males, while in females, only long-term social isolation decreased it. Pain threshold was decreased in both protocols of social isolation in both sexes. OCD-like behavior was increased in both protocols of social isolation in both sexes. Immobility was only decreased in socially isolated female rats. Overall, the findings suggest that social isolation is associated with sex- and protocol-dependent behavioral alterations accompanied by changes in DAT protein levels in the medial prefrontal cortex. In sum, we showed the potential role of DAT in the deleterious effects of social isolation, with sex- and duration-dependent effects of social isolation and DAT.<\/jats:p>","DOI":"10.1038\/s41598-026-48488-1","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T08:17:21Z","timestamp":1777277841000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-dependent effects of short- and long-term social isolation on behavior and medial prefrontal DAT in rats"],"prefix":"10.1038","volume":"16","author":[{"given":"Negin","family":"Marghoob","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Batool Ghorbani","family":"Yekta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"48488_CR1","doi-asserted-by":"publisher","first-page":"102060","DOI":"10.1016\/j.lmot.2024.102060","volume":"88","author":"H Karimi","year":"2024","unstructured":"Karimi, H. et al. 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