title: Xylazine Activates Adenosine Monophosphate-Activated Protein Kinase Pathway in the Central Nervous System of Rats.
abstract: Xylazine is a potent analgesic extensively used in veterinary and animal experimentation. Evidence exists that the analgesic effect can be inhibited using adenosine 5'-monophosphate activated protein kinase (AMPK) inhibitors. Considering this idea, the aim of this study was to investigate whether the AMPK signaling pathway is involved in the central analgesic mechanism of xylazine in the rat. Xylazine was administrated via the intraperitoneal route. Sprague-Dawley rats were sacrificed and the cerebral cortex, cerebellum, hippocampus, thalamus and brainstem were collected for determination of liver kinase B1 (LKB1) and AMPKα mRNA expression using quantitative real-time polymerase chain reaction (qPCR), and phosphorylated LKB1 and AMPKα levels using western blot. The results of our study showed that compared with the control group, xylazine induced significant increases in AMPK activity in the cerebral cortex, hippocampus, thalamus and cerebellum after rats received xylazine (P < 0.01). Increased AMPK activities were accompanied with increased phosphorylation levels of LKB1 in corresponding regions of rats. The protein levels of phosphorylated LKB1 and AMPKα in these regions returned or tended to return to control group levels. However, in the brainstem, phosphorylated LKB1 and AMPKα protein levels were decreased by xylazine compared with the control (P < 0.05). In conclusion, our data indicates that xylazine alters the activities of LKB1 and AMPK in the central nervous system of rats, which suggests that xylazine affects the regulatory signaling pathway of the analgesic mechanism in the rat brain.
authors.affiliation: Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Xing-Xing
authors.initials: XX
authors.lastname: Shi
authors.affiliation: Department of Veterinary Medicine, Jilin Agriculture Science and Technology College, Jilin, Jilin Province, People's Republic of China.
authors.forename: Bai-Shuang
authors.initials: BS
authors.lastname: Yin
authors.affiliation: Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Li-Xue
authors.initials: LX
authors.lastname: Su
authors.affiliation: Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Fan
authors.affiliation: Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Wang
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000263:Adenylate Kinase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation; D008297:Male; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014991:Xylazine / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D014991:Xylazine; D017346:Protein Serine-Threonine Kinases; C488755:Stk11 protein, rat; D000091162:AMP-Activated Protein Kinase Kinases; D000263:Adenylate Kinase