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Here, we examined the effects of opioid withdrawal on BBB and BSCB integrity by measuring extravascular levels of peripherally injected dyes \u2013 Evans Blue (high molecular weight) and sodium fluorescein (NaFl, low molecular weight) \u2013 in the brain and spinal cord. In morphine-dependent male and female mice, repeated naloxone challenge induced robust withdrawal behaviors concomitant with region specific dye extravasation. In a fixed dose morphine paradigm, Evans Blue extravasation was highest within the cortex, hippocampus, cerebellum, and brainstem (pons and medulla) in male mice, and in the hypothalamus in female mice. By contrast, NaFl extravasation remained unchanged in both sexes. In an escalating dose morphine paradigm, Evans Blue extravasation was most prominent in the brainstem (pons and medulla) of both sexes, as well as in the lumbar of male mice and cervical spinal cord of female mice. NaFl extravasation in these regions was unchanged in male but reduced in female mice. These findings suggest that repeated opioid withdrawal alters permeability of the BBB and BSCB in discrete regions of the brain and spinal cord.<\/jats:p>","DOI":"10.1186\/s13041-025-01231-9","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T17:00:58Z","timestamp":1751907658000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Repeated naloxone-induced morphine withdrawal alters blood brain barrier and blood spinal cord barrier integrity in mice"],"prefix":"10.1186","volume":"18","author":[{"given":"Yuta","family":"Kohro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig E.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuan","family":"Trang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"1231_CR1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","volume":"37","author":"NJ Abbott","year":"2010","unstructured":"Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ. 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