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.

Comparative Effect of Propofol and Thiopentone Sodium in Sheep Sedated with Xylazine Hydrochloride

“…Administration of xylazine significantly decresased (P< 0.01) the pulse, respiratory rates and body temaperature. Significant decrease in pulse and not respiratory rates after pre-anaesthetic administration of alpha 2 -agoinst have been reported by other researchers in sheep (Mather et al, 2004) and in goats (Shi et al, 2016). Significant changes in the body temperature after xylazine administration in sheep have also been reported by others in sheep and in goats (Okwudili et al, 2014).…”

“…Xylazine hydrochloride is clinically used for sedative, analgesic and muscle relaxant properties during minor surgical and diagnostic procedures (Clarke and Hall, 1990). Xylazine is highly lipophilic nature and directly stimulates the central α2 adrenergic receptors and leads to a decrease in neurotransmission of norepinephrine and dopamine in the central nervous system (Shi et al, 2016). In veterinary anesthesia, it is a very common procedure of combination therapy and xylazine is often used in combination with ketamine because xylazine reduces the required dose of anaesthetic.…”

Anesthetic protocols for urodynamic studies of the lower urinary tract in small rodents—A systematic review

“…It is rapidly absorbed following intramuscular (i.m.) administration [ 36 , 37 ]. Xylazine is used in a variety of species including the rat and mouse [ 38 , 39 ] in conjunction with ketamine, to eliminate muscle rigidity [ 15 , 17 ].…”

Effects of tiletamine-xylazine-tramadol combination and its specific antagonist on AMPK in the brain of rats

“…The difference in the mRNA expression of AMPKα1 and AMPKα2 in the cerebellum and hippocampus indicated that the antagonists had no effect on AMPKα1 in these regions. One cause may be that the content in the brain of AMPKα2 is higher than that of the α1 subunit (28). Another reason may be that the nuclear localisation complex may also regulate gene expression when a stress response to ATP depletion occurs in the organism (29).…”