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The Dipeptide Mimetic of the Neurotrophin-3 Loop 4, Compound GTS-302, Exhibits Antidepressant-Like Activity in a Mouse Social Defeat Stress Model

P. Y. Povarnina, D. M. Nikiforov, T. A. Antipova, I. O. Logvinov, S. V. Nikolaev, A. V. Tarasiuk, N. M. Sazonova, T. A. Gudasheva*, V. L. Dorofeev

Federal State Budgetary Scientific Institution “Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies”, Moscow, Russia.

*Corresponding author: T. A. Gudasheva

Published: 10 May 2024 How to cite this paper


Experimental and clinical data indicate the involvement of neurotrophin-3 (NT-3) in the pathogenesis of depression. A dimeric dipeptide mimetic of the NT-3 loop 4, bis-(N-gamma-hydroxybutyryl-L-glutamyl-L-asparagine) hexamethylenediamide (GTS-302), demonstrating antidepressant-like activity in the forced swimming test in mice (0.5-10 mg/kg, ip), was created at the Research Zakusov Institute of Pharmacology. The aim of this study was to investigate the antidepressant-like activity of the dipeptide GTS-302 in an experimental model of depression. Male C57Bl/6 mice were exposed to a 10-day social defeat stress. They received daily ip injections of the dipeptide GTS-302 at a dose of 1 mg/kg for the entire duration of the stress period. Following the stress, the sucrose preference test was conducted to assess anhedonia. Hippocampal tissue was then collected for the analysis of synaptic proteins (synaptophysin, PSD-95) and BDNF levels using Western blot analysis. In stressed mice, sucrose preference decreased by 16% compared to non-stressed controls, accompanied by an 18% reduction in hippocampal BDNF levels. Treatment with compound GTS-302 nearly completely counteracted these impairments. Therefore, the dipeptide mimetic of NT-3, GTS-302, holds promise as a potential antidepressant.

KEYWORDS: NT-3, dimeric dipeptide mimetic, GTS-302, depression, social defeat stress, anhedonia, BDNF


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How to cite this paper

P. Y. Povarnina, D. M. Nikiforov, T. A. Antipova, I. O. Logvinov, S. V. Nikolaev, A. V. Tarasiuk, N. M. Sazonova, T. A. Gudasheva, V. L. Dorofeev. The Dipeptide Mimetic of the Neurotrophin-3 Loop 4, Compound GTS-302, Exhibits Antidepressant-Like Activity in a Mouse Social Defeat Stress Model. International Journal of Medicine Frontiers, 2024, 7(1), 1-9.

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