Xylazine regulates the release of glycine and aspartic acid in rat brain

Abstract

IntroductionXylazine, 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 MethodsWistar 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, 35μg/mL, and 45 μg/mL of xylazine. Test methods were based on the enzyme-linked immunosorbent assays (ELISA).ResultsDuring 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.ConclusionThe 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.

Physiological and Biochemical Markers of the Sex-Specific Sensitivity to Epileptogenic Factors, Delayed Consequences of Seizures and Their Response to Vitamins B1 and B6 in a Rat Model

“…Animals were killed by decapitation according to the schemes from Supplementary Figure S1 , as usage of anesthetics was incompatible with our study of the brain biochemical changes. A long-standing research has established multiple interferences of different anesthetics with metabolic and signaling pathways [ 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ]. In view of strong interactions of anesthetics with the mitochondrial function [ 56 , 58 , 59 ], neurotransmitter levels [ 58 , 61 , 62 , 63 , 64 ] and action of neuroprotectants [ 61 , 64 ], all studied in our work, euthanasia by decapitation was chosen as the most suitable method for our studies on adult animals, in accordance with existing recommendations [ 63 , 64 , 65 ].…”

“…A long-standing research has established multiple interferences of different anesthetics with metabolic and signaling pathways [ 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ]. In view of strong interactions of anesthetics with the mitochondrial function [ 56 , 58 , 59 ], neurotransmitter levels [ 58 , 61 , 62 , 63 , 64 ] and action of neuroprotectants [ 61 , 64 ], all studied in our work, euthanasia by decapitation was chosen as the most suitable method for our studies on adult animals, in accordance with existing recommendations [ 63 , 64 , 65 ]. Given that the other animals are not in the decapitation room, cutting off the head using guillotine (OpenScience, Moscow, Russia) is considered one of the least stressful method to kill the animals [ 63 , 64 , 65 , 66 ].…”

Increasing Inhibition of the Rat Brain 2-Oxoglutarate Dehydrogenase Decreases Glutathione Redox State, Elevating Anxiety and Perturbing Stress Adaptation

“…Twenty-four hours after the substance administration, the rats were subjected to physiological tests and killed by decapitation as described before [82,89]. Taking into account that anaesthetics influence mitochondrial and brain function [88,[93][94][95][96][97][98], rats were killed by decapitation with a guillotine (OpenScience, Moscow, Russia) without anaesthetics. Such a method is in line with the latest recommendations and guidelines [88,97,99].…”

Neurotoxicity of xylazine in chicks

“…For the first time in our study, the concentration of glycine and glutamate in plasma was measured after 60 and 90 minutes of xylazine injection. In our study, conducted during anesthesia with xylazine, we noticed an increase in glycine concentration in the plasma and a decrease in the concentration of glutamate after 90 minutes of injection, and the concentrations changed irregularly (29).…”

“…The high glycine concentrations in the plasma may be due to the role of xylazine in promoting the synthesis and release of glycine, which reduces the excitability of neurons and thus leads to anesthesia (29). The decrease in the concentration of glutamate is due to the effect of xylazine in inhibiting the synthesis of glutamate, which reduces the excitatory neurotransmitter and ultimately reduces the stimulation of neurons and the production of an anesthetic effect (30).…”