Abstract—In mammals, chronic alcohol exposure disrupts the balance between excitatory and inhibitory neurotransmitter amino acids, including a decrease in GABAergic inhibitory function and an increase in glutamatergic excitatory activity. The effectiveness of the peptide anxiolytic selank against ethanol withdrawal anxiety and memory impairments was shown previously. In order to study the neurochemical mechanism of action of selank in an alcohol withdrawal model, we evaluated its effect on the content of neurotransmitter amino acids in various brain structures in rats. The experiments were performed with outbred male rats that consumed 10% ethanol solution as the only source of liquid for 30 weeks. During ethanol exposure, a subgroup of animals with a high level of motivation to consume alcohol was identified, and most of the work was carried out on these rats. Selank at an anxiolytic dose of 0.3 mg/kg was administered intraperitoneally for 7 days during ethanol withdrawal. Decapitation was performed 24 h after the last injection. In ex vivo experiments using HPLC/FD, selank was shown to prevent the ethanol withdrawal induced increase in the content of aspartic acid, glycine, and taurine in the hypothalamus, GABA in the n. accumbens, and aspartic acid and glycine in the striatum. These data indicate that during the alcohol deprivation period, the pharmacological effects of selank are associated with a decrease in the level of inhibitory neurotransmitter amino acids.
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The study was performed within the scope of project no. 0521-2019-0006.
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Ethical approval. Organizing and conducting the experiments was in compliance with “Rules of good laboratory practice of the Russian Federation” approved by the Order of the Ministry of Health of the Russian Federation no. 199n of April 1, 2016. The animals were maintained in accordance with SP 2.2.1.3218-14 “Sanitary and epidemiological requirements for arrangement, equipment and maintenance of biological clinics (vivariums)” of August 29, 2014 no. 51. The experimental procedures were approved by the Bioethics Commission of the Zakusov Research Institute of Pharmacology.
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Kolik, L.G., Nadorova, A.V., Kon’kov, V.G. et al. Heptapeptide Analogue of Tuftsin Prevents the Increase in the Content of Inhibitory Amino Acids in the Brain When Modeling Alcohol Withdrawal in Rats. Neurochem. J. 15, 196–202 (2021). https://doi.org/10.1134/S1819712421020082
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DOI: https://doi.org/10.1134/S1819712421020082