{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:31:39Z","timestamp":1785429099541,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32273078"],"award-info":[{"award-number":["32273078"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["32273078"],"award-info":[{"award-number":["32273078"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province of China","doi-asserted-by":"crossref","award":["LH2023C027"],"award-info":[{"award-number":["LH2023C027"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Young Talents Program of Northeast Agricultural University","award":["23YJQA02"],"award-info":[{"award-number":["23YJQA02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Xylazole is a sedative and analgesic agent widely used in Chinese veterinary practice, valued for its convenient administration and effectiveness. This study aimed to clarify its mechanism of action by investigating the effects on cAMP and monoamine neurotransmitters using both in vitro and in vivo rat models. In rat cortical neurons, Xylazole increased cAMP levels in a concentration- and time-dependent manner, transiently increased extracellular DA levels, which subsequently declined, consistently reduced extracellular NE levels, and enhanced extracellular 5-HT along with its metabolite 5-HIAA. In contrast, in vivo administration in adult rats reduced cAMP, DA, and NE levels across multiple brain regions, including the cerebrum, hippocampus, and brainstem, while increasing 5-HT and 5-HIAA. Notably, in the cerebellum group, cAMP was elevated after drug washout, a pattern not observed in the other brain regions. These findings reveal a striking divergence: in P7 cortical neurons, Xylazole triggers an \u03b12-adrenoceptor-dependent cAMP elevation, whereas in adult brain regions, a high concentration of locally delivered Xylazole leads to predominantly inhibitory cAMP changes, with a notable delayed increase in the cerebellum. Because of the non-physiological concentration used in reverse microdialysis, the in vivo neurochemical patterns should be regarded as exploratory regional responses, not as evidence of specific receptor-mediated mechanisms.<\/jats:p>","DOI":"10.3390\/cells15121120","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T09:49:55Z","timestamp":1782121795000},"page":"1120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Xylazole on cAMP and Monoamine Neurotransmitters in Rats: In Vitro and In Vivo"],"prefix":"10.3390","volume":"15","author":[{"given":"Xingyu","family":"Hou","sequence":"first","affiliation":[{"name":"Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianwen","family":"Ma","sequence":"additional","affiliation":[{"name":"Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wu","sequence":"additional","affiliation":[{"name":"Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7671-6908","authenticated-orcid":false,"given":"Honggang","family":"Fan","sequence":"additional","affiliation":[{"name":"Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7876-5578","authenticated-orcid":false,"given":"Shuai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1111\/j.1467-2995.2010.00538.x","article-title":"Effects of xylazole alone and in combination with ketamine on the metabolic and neurohumoral responses in healthy dogs","volume":"37","author":"Changmin","year":"2010","journal-title":"Vet. 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