The effect of GHK-PGP peptide and its analogues on the rat’s behavior in the forced swimming test

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Abstract

Introduction. The Gly-His-Lys (GHK) peptide, which is a fragment of type I collagen, has a wide range of biological effects, including neurotropic ones, and has an anxiolytic and analgesic effect. However, GHK is susceptible to proteases and various proline-containing amino acid sequences were added to the C-terminus to increase the duration of its effects.

Purpose of the study. Study of the behavior of rats in the forced swimming test using the GHK-PGP peptide and its structural analogs.

Material and methods. The experiments were performed on 200 male Wistar rats weighing 170–190 g. The work used peptides synthesized in the Laboratory of Molecular Pharmacology of Peptides of the National Research Center “Kurchatov Institute” (GHK, Pro-Gly-Pro (PGP), Gly-His-Lys-Pro-Gly-Pro (GHK-PGP), Gly-His-Lys-Gly-Pro (GHK-GP), Gly-His-Lys-Pro (GHK-P), Gly-His-Lys-Val-Glu-Pro (GHK-VEP)), which were administered intraperitoneally 15 min before the experiment at doses of 0,5; 5,0 and 50,0 μg/kg. Animal behavior was assessed using a forced swim test.

Results. GHK at a dose of 5,0 μg / kg caused a decrease in motor activity, and the PGP peptide at doses of 0,5 and 50,0 μg/kg had a pronounced antidepressant effect. GHK-PGP had an antidepressant effect only at a dose of 5,0 μg / kg. Thus, in the total GHK-PGP molecule, the PGP peptide neutralized the effect of GHK and was its structural part, determining this type of biological activity. GHK-GP had no effects at all doses. The GHK-VEP peptide had an antidepressant effect at a dose of 0,5 μg / kg.

Conclusion. GHK-PGP and its structural modifications using proline-containing amino acid sequences affect behavior in the forced swim test in rats, while the anxiolytic effect of GHK is neutralized with the appearance of an antidepressant effect.

About the authors

Marina E. Alferova

Kursk State Medical University

Author for correspondence.
Email: mmarinusya@mail.ru
ORCID iD: 0009-0005-8362-3709

Assistant Professor, Department of Pathophysiology

Russian Federation, Karl Marx Str, 3, Kursk, 305041

Igor I. Bobyntsev

Kursk State Medical University

Email: bobig@mail.ru
ORCID iD: 0000-0001-7745-2599

Head of the Department of Pathophysiology, Director of the Research Institute of General Pathology; Doctor of Medical Sciences, Associate Professor

Russian Federation, Karl Marx Str, 3, Kursk, 305041

Anton O. Vorvul

Kursk State Medical University

Email: vorvul1996@mail.ru
ORCID iD: 0000-0002-1529-6014

Senior Lecturer, Department of Pathophysiology; Candidate of Medical Sciences

Russian Federation, Karl Marx Str, 3, Kursk, 305041

Anna N. Tenkova

Kursk State Medical University

Email: tenkova.85@mail.ru
ORCID iD: 0009-0007-8699-8041

Assistant Professor, Department of Human Anatomy

Russian Federation, Karl Marx Str, 3, Kursk, 305041

Liudmila A. Andreeva

National Research Centre “Kurchatov Institute”

Email: landr@img.ras.ru
ORCID iD: 0000-0002-3927-8590

Deputy Head of the Laboratory of Molecular Pharmacology of Peptides

Russian Federation, Academician Kurchatov square, 1, Moscow, 123182

Nikolai F. Myasoedov

National Research Centre “Kurchatov Institute”

Email: nfm@img.ras.ru
ORCID iD: 0000-0003-1294-102X

Head of the Laboratory of Molecular Pharmacology of Peptides; Doctor of Chemical Sciences, Professor, Academician of the Russian Academy of Sciences

Russian Federation, Academician Kurchatov square, 1, Moscow, 123182

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