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However, the recent use of xylazine as adulterant with opioids has created a public health emergency due to an increased number of addiction-related deaths and adverse effects. As a result, xylazine\u2019s pharmacological profile has been revisited, and it has been found to act as a full agonist at \u03ba-opioid receptors. Because increased urine output is a well-established effect of \u03ba-opioid receptor agonists, we determined if \u03ba-opioid receptors are involved in xylazine-induced diuresis. Adult male Sprague\u2013Dawley rats were used. A dose\u2013response curve was first established through systemic administration of xylazine. Rats were injected with xylazine (1.25, 2.5, or 5\u00a0mg\/kg) or saline and then placed into metabolic cages for 2\u00a0h for urine collection. Xylazine doses of 2.5 and 5\u00a0mg\/kg significantly increased urine output compared to saline-injected rats, indicating that xylazine caused diuresis. Next, rats were pretreated with saline; a \u03ba-opioid receptor antagonist, 5\u2032-guanidinonaltrindole (5\u2032-GNTI) (0.01\u20130.1\u00a0mg\/kg); or an \u03b12-adrenoceptor antagonist, yohimbine (0.3\u20131\u00a0mg\/kg). Thirty minutes later, rats were injected with saline or a fixed dose of xylazine (2.5\u00a0mg\/kg) and urine was collected for 2\u00a0h. Pretreatment with either 5\u2032-GNTI or yohimbine significantly decreased xylazine-induced diuresis. Our findings suggest that xylazine-induced diuresis is mediated by both \u03ba-opioid receptors and \u03b12-adrenoceptors, highlighting the importance of considering \u03ba-opioid receptor activation when evaluating in vivo pharmacological effects of xylazine.<\/jats:p>","DOI":"10.1007\/s00210-026-05565-6","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:20:11Z","timestamp":1781670011000},"page":"20069-20073","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Xylazine-induced diuresis in rats is attenuated by \u03ba-opioid receptor and \u03b12-adrenoceptor antagonists"],"prefix":"10.1007","volume":"399","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4510-392X","authenticated-orcid":false,"given":"Saadet","family":"Inan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Rawls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"5565_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2023.110993","volume":"253","author":"P Acosta-Mares","year":"2023","unstructured":"Acosta-Mares P, Violante-Soria V, Browne T Jr, Cruz SL (2023) Xylazine potentiates the lethal but not the rewarding effects of fentanyl in mice. 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