Anxiolytic Effects of GHK-GP Peptide and its Structural Analogues in Elevated Plus Maze Test

Regulatory peptides are currently attracting research interest due to their potential application in the creation of new drugs. Among them, Gly-His-Lys (GHK) peptide seems to be promising. However, its high susceptibility to proteases requires the development of various methods for its protection, such as the addition of Pro-Gly-Pro (PGP), as well as various proline-containing amino acid sequences, to the C-terminus of GHK. The biological effects of the newly formed oligopeptides can differ significantly from those of GHK. In this work, we investigate the anxiolytic effects of the GHK-GP (Gly-His-Lys-Gly-Pro) peptide and its structural analogs in an elevated plus maze test. The experiments involved 200 male Wistar rats and the following peptides: GHK, PGP, GHK-PGP, GHK-GP, GHK-P (Gly-His-Lys-Pro), and GHK-VEP (Gly-HisLys-Val-Glu-Pro). The peptides were administered intraperitoneally at doses of 0.5, 5.0, and 50.0 μg/kg. Animals in the control group were administered equivalent volumes of saline. Anxiolytic activity under non-punishable conditions was assessed using an elevated plus maze. GHK peptide was revealed to exhibit anxiolytic activity at all the doses studied. PGP and GHK-PGP peptides did not exhibit anxiolytic action in this experiment. Thus, it can be assumed that PGP peptide completely neutralizes the anxiolytic effect of GHK. In addition, the anxiolytic effect was completely absent in the GHK-P and GHKVEP peptides, which also indicates the blocking of the anxiolytic effect of GHK due to the attachment of proline and the amino acid sequence Val-Glu-Pro to its C-terminus. The GHK-GP peptide, conversely, showed a pronounced anxiolytic activity at doses of 0.5 and 5.0 μg/kg, which may indicate the potentiation of the anxiolytic effect of GHK due to the attachment of the Gly-Pro dipeptide, as well as the direct anxiolytic effect of the Gly-Pro peptide per se through its direct or indirect neurotropic action.

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