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.
Highlights
ObjectivesConsidering 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 is exclusively used as a sedative, analgesic, and muscle relaxant in veterinary medicine, and is marketed as Rompun, Anased, Sedazine, Megaxilor, Paxman and Chanazine [1, 2].PLOS ONE | DOI:10.1371/journal.pone.0153169 April 6, 2016Xylazine Activates AMPK Pathway in Rats
The results of our study showed that, compared with the sedative state, xylazine induced a significant decrease in the mRNA levels of liver kinase B1 (LKB1) in the brainstem at 40 min after rats received xylazine, whereas a significant increase was observed in the cerebral cortex, hippocampus, thalamus, and cerebellum, suggesting that a region-dependent regulation mechanism may modulate LKB1 gene expression at the transcriptional level in rats exposed to xylazine
Summary
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. To elucidate the mechanisms involved in intraperitoneal xylazine administration, the goal of the present study was to determine whether the LKB1-AMPK pathway is involved in xylazine-induced sedation in the CNS which would lead us to further understanding in the field of veterinary anaesthesia and analgesia
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