Kashkin V.A. Model of ethanol withdrawal in rats . Laboratory Animals for Science. 2020; 2. https://doi.org/10.29296/2618723X-2020-02-05
The aim of this study was to develop a simple and reproducible protocol for the formation of alcohol withdrawal syndrome in rats. Experimental modeling of alcohol withdrawal was carried out by forced intragastric administration of 25% ethanol in a daily dose of 5 g/kg during 14 days. The success of pathology formation was assessed using behavioral analysis based on the data of emotional, stereotypic, and motor components of the behavior of experimental animals in the “Open field” test, as well as the results of evaluating the severity of the generalized motor activation reaction (audiogenic startle response) in rats. Instrumental assessment methods included monitoring systolic blood pressure (SBP), heart rate, as well as the state of the enzymatic blood system and the activity of the lipid peroxidation caused by the abolition of chronic alcohol consumption in rats.
Manifestations of the alcohol withdrawal syndrome were accompanied by behavioral stress, which was associated with an increase in anxiety and an increase in the reaction of generalized motor activation after presentation of a short audiogenic stimulus (startle response), an increase in SBP by an average of 20 mmHg. Biochemical analysis of the enzymatic activity showed an increase in the concentration of creatinine and the activity of AST and LDH in blood plasma. The alcohol withdrawal was indicated by a decrease in the activity of enzymes of the antioxidant system, such as superoxide dismutase, glutathione peroxidase, and glutathione transferase, which are signs of the development of oxidative stress during the chronic exposure to alcohol.
Thus, the long forced administration of 25% ethanol allowed the formation of a pathology that was characterized by symptoms of withdrawal without lethal cases. The protocol includes the recommended evaluation methods that allow identifying the effectiveness of the tested drugs for the prevention and relief of manifestations of the alcohol withdrawal in the experiment.
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Acknowledgements. The study reported by the Research and manufacturing company «Home оf Pharmacy». I also express my appreciation to Faustova N.M., PhD, for conducting biochemical studies.