Introduction: Xylazine, a type of α2-adrenoceptors, is a commonly used drug in veterinary medicine. Xylazine-induced changes in the content of amino acid neurotransmitters – glycine (Gly) and aspartic acid (Asp), in different brain regions and neurons were studied.
Material and Methods: Wistar rats were administered 50 mg/kg or 70 mg/kg of xylazine by intraperitoneal injection. In addition, in vitro experiments were conducted, in which neurons were treated with 15 μg/mL, 25 μg/mL, 35 μg/mL, and 45 μg/mL of xylazine. Test methods were based on the enzyme-linked immunosorbent assays (ELISA).
Results: During anaesthesia, Asp levels in each brain area were significantly lower compared to the control group. Except for the cerebrum, levels of Gly in other brain areas were significantly increased during the anaesthesia period. In vitro, xylazine-related neuron secretion of Gly increased significantly compared to the control group at 60 min and 90 min. Moreover, xylazine caused a significant decrease in the levels of Asp secreted by neurons at 20 min, but gradually returned to the level of the control group.
Conclusion: The data showed that during anaesthesia the overall levels of Asp decreased and overall levels of Gly increased. In addition, the inhibitory effect of xylazine on Asp and the promotion of Gly were dose-dependent. Our data showed that different effects of xylazine on excitatory and inhibitory neurotransmitters provided a theoretical basis for the mechanism of xylazine activity in clinical anaesthesia.
1. Chen L.J., Sun B.H., Cao Y., Yao H.D., Qu J.P., Liu C., Xu S.W., Li S.: The effects of avermectin on amino acid neurotransmitters and their receptors in the pigeon brain. Pestic Biochem Physiol 2014, 110, 13–19.
2. Chen X., Yan R., Bai Z., Ma H.: Enhanced sedative efficacy and delayed recovery in propofol anesthesia in a rat model of hepatic cirrhosis. Int J Clin Exp Med 2015, 8, 5723–5730.
3. Cui T., Qiu H.M., Huang D., Zhou Q.X., Fu X.Y., Li H.Y., Jiang X.H.: Abnormal levels of seven amino neurotransmitters in depressed rat brain and determination by HPLC-FLD. Biomed Chromatogr 2017, 31, e3937.
4. Erhan E., Terzi S., Celiker M., Yarali O., Cankaya M., Cimen F.K., Malkoc I., Suleyman B.: Effect of Hippophae rhamnoides extract on oxidative oropharyngeal mucosal damage induced in rats using methotrexate. Clin Exp Otorhinolaryngol 2017, 10, 181–187.
5. Forrester M.B.: Xylazine exposures reported to Texas Poison Centers. J Emerg Med 2016, 51, 389–393.
6. Fu B., Wang Y., Yang H., Yu T.: Effects of etomidate on GABAergic and glutamatergic transmission in rat thalamocortical slices. Neurochem Res 2016, 41, 3181–3191.
7. Garlet Q.I., Pires L.D.C., Milanesi L.H., Marafiga J.R., Baldisserotto B., Mello C.F., Heinzmann BM.: (+)-Dehydrofukinone modulates membrane potential and delays seizure onset by GABAa receptor-mediated mechanism in mice. Toxicol Appl Pharmacol 2017, 332, 52–63.
8. Grasshoff C., Antkowiak B.: Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats. Br J Anaesth 2006, 97, 687–694.
9. Huang L., Hayes S., Yang G.: Long-lasting behavioral effects in neonatal mice with multiple exposures to ketamine–xylazine anesthesia. Neurotoxicol Teratol 2017, 60, 75–81.
10. Ismail Z.B.: Epidural analgesia in cattle, buffalo, and camels. Vet World 2016, 9, 1450–1455.
11. Krol E., Dziubinska H., Trebacz K., Koselski M., Stolarz M.: The influence of glutamic and aminoacetic acids on the excitability of the liverwort Conocephalum conicum. J Plant Physiol 2007, 164, 773–784.
12. Li C., Qi F., Liu T., Wang H., Wang P.Z.: Improved cuff technique for establishing a mouse-rat heterotopic cardiac xenotransplantation model. Transplant Proc 2015, 47, 2026–2031.
13. Loscher W., Hoffmann K., Twele F., Potschka H., Tollner K.: The novel antiepileptic drug imepitoin compares favourably to other GABA–mimetic drugs in a seizure threshold model in mice and dogs. Pharmacol Res 2013, 77, 39–46.
14. Lu H., Xu T.L.: The general anesthetic pentobarbital slows desensitization and deactivation of the glycine receptor in the rat spinal dorsal horn neurons. J Biol Chem 2002, 277, 41369–41378.
15. Merino J.J., Arce C., Naddaf A., Bellver-Landete V., Oset-Gasque M.J., Gonzalez MP.: The nitric oxide donor SNAP–induced amino acid neurotransmitter release in cortical neurons. Effects of blockers of voltage–dependent sodium and calcium channels. PLoS One 2014, 9, e90703.
16. Minami K., Sudo Y., Yokoyama T., Ogata J., Takeuchi M., Uezono Y.: Sevoflurane inhibits the micro-opioid receptor function expressed in Xenopus oocytes. Pharmacology 2011, 88, 127–132.
17. Moly P.K., Ikenaga T., Kamihagi C., Islam A.F., Hatta K.: Identification of initially appearing glycine-immunoreactive neurons in the embryonic zebrafish brain. Dev Neurobiol 2014, 74, 616–632.
18. Moran T.D., Colmers W.F., Smith PA.: Opioid-like actions of neuropeptide Y in rat substantia gelatinosa: Y1 suppression of inhibition and Y2 suppression of excitation. J Neurophysiol 2004, 92, 3266–3275.
19. Petroff O.A.: GABA and glutamate in the human brain. Neuroscientist 2002, 8, 562–573.
20. Potliya S., Kumar A., Kumar S., Singh S., Kumar S.: Evaluation of efficacy and safety of glycopyrrolate – xylazine – propofol anesthesia in buffalo calves. Vet World 2015, 8, 251–256.
21. Su Z., Xu S., Chen T., Chen J.: Dexmedetomidine protects spatial learning and memory ability in rats. J Renin Angiotensin Aldosterone Syst 2015, 16, 995–1000.
22. Sun J.L., Duan S.M., Wang J., Zeng Y.M.: Effects of isoflurane on amino acid neurotransmitter levels in rat cerebral cortex, hippocampus and spinal cord. Chinese J Anesthesiol 2002, 22, 171–173.
23. Szpetnar M., Luchowska-Kocot D., Boguszewska-Czubara A., Kurzepa J.: The influence of manganese and glutamine intake on antioxidants and neurotransmitter amino acids levels in rats' brain. Neurochem Res 2016, 41, 2129–2139.
24. Ugale V.G., Bari S.B.: Identification of potential Gly/NMDA receptor antagonists by cheminformatics approach: a combination of pharmacophore modelling, virtual screening and molecular docking studies. SAR QSAR Environ Res 2016, 27, 125–145.
25. Wakita M., Kotani N., Shoudai K., Yamaga T., Akaike N.: Modulation of inhibitory and excitatory fast neurotransmission in the rat CNS by heavy water (D2O). J Neurophysiol 2015, 114, 1109–1118.
26. Wang J.X., Yang X., Zhang J.J., Zhou T.T., Zhu Y.L., Wang L.Y.: Effects of Shaoyao Gancao decoction on contents of amino acids and expressions of receptors in brains of spastic paralysis rats. Zhongguo Zhong Yao Za Zhi 2016, 41, 1100–1106.
27. Wang X.F., Luo X.L., Liu W.C., Hou B.C., Huang J., Zhan Y.P., Chen S.B.: Effect of dexmedetomidine priming on convulsion reaction induced by lidocaine. Medicine (Baltimore) 2016, 95, e4781.
28. Wang Y.X., Zhang F., Ma X.L., He C.C., Tian K., Wang H.G., An D., Heng B., Xie L.H., Liu Y.Q.: Oxygen-glucose deprivation enhancement of cell death/apoptosis in PC12 cells and hippocampal neurons correlates with changes in neuronal excitatory amino acid neurotransmitter signaling and potassium currents. Neuroreport 2016, 27, 617–626.
29. Yang G., Chang P.C., Bekker A., Blanck T.J., Gan W.B.: Transient effects of anesthetics on dendritic spines and filopodia in the living mouse cortex. Anesthesiology 2011, 115, 718–726.
30. Zahn P.K., Sluka K.A., Brennan T.J.: Excitatory amino acid release in the spinal cord caused by plantar incision in the rat. Pain 2002, 100, 65–76.