PMID- 30956255 OWN - NLM STAT- MEDLINE DCOM- 20191122 LR - 20200225 IS - 1881-7122 (Electronic) IS - 1341-1357 (Print) IS - 0007-5124 (Linking) VI - 68 IP - 3 DP - 2019 Aug 14 TI - Molecular mechanisms of the sedation and analgesia induced by xylazine on Wistar rats and PC12 cell. PG - 351-360 LID - 10.1538/expanim.18-0167 [doi] AB - In veterinary clinics, xylazine is commonly used as a sedative, analgesic agent that produces muscle relaxation. In this study, we aimed to explore the mechanism of action of xylazine both in vivo and in vitro. After determing the optimal dose of xylazine, 35 male Wistar rats were divided into seven groups (n=5 per group), including a control group (saline) and xylazine administration groups. Then, at six time points after xylazine administration indicators were evaluated for changes. Moreover, PC12 cells were co-cultured with xylazine, and extracellular regulated protein kinase (ERK) siRNA and protein kinase A (PKA) siRNA were transfected into cells to identify changes of relevant indicators. Our data showed that xylazine influenced the level of adenosine triphosphate (ATP) ase and cyclic adenosine monophosphate (cAMP), and regulated the expression of GluR1, ERK, PKA, cAMP-response element binding protein (CREB), and brain derived neurotrophic factor (BDNF) in the nervous system. However, xylazine did not significantly affect the expression of GluR2 and protein kinase C (PKC). Together, these results indicated that xylazine might exert sedation and analgesia by regulating the PKA/ERK/CREB signaling pathway. FAU - Zhao, Jinghua AU - Zhao J AD - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University, No. 600 Chang Jiang Road, Xiangfang District, Harbin 150030, China. FAU - Zhang, Yiming AU - Zhang Y AD - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University, No. 600 Chang Jiang Road, Xiangfang District, Harbin 150030, China. FAU - Liu, Wenhan AU - Liu W AD - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University, No. 600 Chang Jiang Road, Xiangfang District, Harbin 150030, China. FAU - Chen, Yu AU - Chen Y AD - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University, No. 600 Chang Jiang Road, Xiangfang District, Harbin 150030, China. FAU - Chang, Daiyue AU - Chang D AD - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University, No. 600 Chang Jiang Road, Xiangfang District, Harbin 150030, China. FAU - Zhang, Xintong AU - Zhang X AD - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University, No. 600 Chang Jiang Road, Xiangfang District, Harbin 150030, China. FAU - Chang, Tian AU - Chang T AD - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University, No. 600 Chang Jiang Road, Xiangfang District, Harbin 150030, China. FAU - Wang, Qi AU - Wang Q AD - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University, No. 600 Chang Jiang Road, Xiangfang District, Harbin 150030, China. FAU - Liu, Tao AU - Liu T AD - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University, No. 600 Chang Jiang Road, Xiangfang District, Harbin 150030, China. FAU - Gao, Li AU - Gao L AD - Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agriculture University, No. 600 Chang Jiang Road, Xiangfang District, Harbin 150030, China. LA - eng PT - Journal Article DEP - 20190408 PL - Japan TA - Exp Anim JT - Experimental animals JID - 9604830 RN - 0 (Analgesics) RN - 0 (Hypnotics and Sedatives) RN - 2KFG9TP5V8 (Xylazine) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) SB - IM MH - Analgesics/*administration & dosage/metabolism MH - Animals MH - Conscious Sedation MH - Cyclic AMP-Dependent Protein Kinases/physiology MH - Dose-Response Relationship, Drug MH - Hypnotics and Sedatives/*administration & dosage/metabolism MH - Interpleural Analgesia MH - MAP Kinase Signaling System/drug effects/physiology MH - Male MH - PC12 Cells MH - Rats/*physiology MH - Rats, Wistar MH - Signal Transduction/*drug effects/physiology MH - Xylazine/*administration & dosage/metabolism PMC - PMC6699970 OTO - NOTNLM OT - PC12 cells OT - analgesia OT - rat OT - sedation OT - xylazine COIS- There is no conflict of interest. EDAT- 2019/04/09 06:00 MHDA- 2019/11/23 06:00 PMCR- 2019/01/01 CRDT- 2019/04/09 06:00 PHST- 2019/04/09 06:00 [pubmed] PHST- 2019/11/23 06:00 [medline] PHST- 2019/04/09 06:00 [entrez] PHST- 2019/01/01 00:00 [pmc-release] AID - 18-0167 [pii] AID - 10.1538/expanim.18-0167 [doi] PST - ppublish SO - Exp Anim. 2019 Aug 14;68(3):351-360. doi: 10.1538/expanim.18-0167. Epub 2019 Apr 8.