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Anxiolytic Effects of Gly-His-Lys Peptide and Its Analogs
Abstract
Intraperitoneal administration of tripeptide Gly-His-Lys to male rats in doses of 0.5, 5, and 50 μg/kg 12 min before the start of the experiment produced an anxiolytic effect in the elevated plus maze test manifested in an increase in the time spent in open arms and shortened time spent in the closed arms. The anxiolytic effect was most pronounced after injection of 0.5 μg/kg peptide and decreased with increasing the dose of the peptide. Replacement of L-lysine with D-lysine in the tripeptide molecule was accompanied by a significant weakening of the neurotropic effects in all studied doses. Attachment of D-alanine to N- or C-terminus of Gly-His-Lys peptide leveled its anxiolytic action in all doses; significant changes in some measures of increased anxiety after administration at 50 μg/kg were found.
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In the citing paper
“GHK reduced pain after thermal injury to rats at a dose of 0.5 milligrams/kg.”
From The Effect of the Human Peptide GHK on Gene Expression Relevant to Nervous System Function and Cognitive Decline (2017) · cites this paper as [52]
In the citing paper
“Within 12 min after intraperitoneal injection, it also increased the amount of time the rats spent exploring more open areas of the maze”
From The Effect of the Human Peptide GHK on Gene Expression Relevant to Nervous System Function and Cognitive Decline (2017) · cites this paper as [52]
In the citing paper
“decreased time spent immobile (the freeze reaction), which indicated reduction of fear and anxiety.”
From The Effect of the Human Peptide GHK on Gene Expression Relevant to Nervous System Function and Cognitive Decline (2017) · cites this paper as [52]
In the citing paper
“It has numerous actions, including wound-healing [2], anti-inflammatory [3], and anti-anxiety [4] activities which may result from the interaction with unidentified receptors.”
From Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate (2020) · cites this paper as [4]
In the citing paper
“GHK has potent anti-pain, anti-anxiety (anxiolytic) and anti-aggression actions.”
From Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data (2018) · cites this paper as [53]
In the citing paper
“When rats are afraid, they try to hide. But within 12 min of intraperitoneal injection of GHK at 0.5 micrograms/kilogram into rats in a testing cage built as a maze, the amount of time the rats spent exploring more open and lighted areas of the maze increased, and the time spent immobile (the freeze reaction) decreased, which indicated a reduction of fear and anxiety [53].”
From Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data (2018) · cites this paper as [53]
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References 6 · Cited by 20
Research works printed but not linked: 7
- I. P. Ashmarin and E. P. Karazeeva, Uspekhi Fiziol. Nauk, 34, No. 1, 14-19 (2003).
- T. A. Voronina and S. B. Seredenin, Guidelines for the Study of Tranquilizing (Anxiolytic) Action of Pharmacological Substances [in Russian], Moscow (2005), pp. 257-258.
- S. V. Koroleva and I. P. Ashmarin, Ross. Fiziol. Zh. Im. I. M. Sechenova, 91, No. 1, 3-11 (2005).
- S. V. Koroleva and N. F. Myasoedov, Uspekhi Fiziol. Nauk, 43, No. 3, 38-47 (2012).
- M. R. Ahmed, S. H. Basha, D. Gopinath, et al., J. Peripher. Nerv. Syst., 10, No. 1, 17-30 (2005). · DOI · Paper page
- H. K. Pyo, H. G. Yoo, C. H. Won, et al., Arch. Pharm. Res., 30, No. 7, 834-839 (2007). · DOI
- M. Smriga, M. Kameishi, H. Uneyama, and K. Torii, J. Nutr., 132, No. 12, 3744-3746 (2002). · DOI
Metadata
- Authors
- Bobyntsev, I. I., Chernysheva, O. I., Dolgintsev, M. E., Smakhtin, M. Y., & Belykh, A. E.
- Affiliations
- Kursk State Medical University (RU)
- ORCID
- Smakhtin, M. Yu.
- Venue
- Bulletin of Experimental Biology and Medicine
- Published
- 2015-04
- Volume
- 158
- Issue
- 6
- Pages
- 726-728
- ISSN
- 0007-4888 (ISSN-L)
- 1573-8221
- OpenAlex
- W1993480017
- Cited by
- 20
- References
- 6
- Citations by year
- 2026: 2 · 2025: 3 · 2022: 5 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 1
- FWCI
- 0.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Bulletin of Experimental Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- tripeptides, anxiolytic effects, anxiety, elevated plus maze, D-lysine, D-alanine, peptide analogues, neurotropic effects, dose-response relationship
- MeSH terms
- Animals, Anxiety, Male, Oligopeptides, Anti-Anxiety Agents, Maze Learning, Rats
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- CoChat. (2026). Citation check: Anxiolytic Effects of Gly-His-Lys Peptide and Its Analogs. https://app.cochat.ai/papers/10.1007/s10517-015-2847-3
- The paper
- Bobyntsev, I. I., Chernysheva, O. I., Dolgintsev, M. E., Smakhtin, M. Y., & Belykh, A. E. (2015). Anxiolytic Effects of Gly-His-Lys Peptide and Its Analogs. Bulletin of Experimental Biology and Medicine. https://doi.org/10.1007/s10517-015-2847-3
