Effect of the dipeptide retro-analog of cholecystokinin tetrapeptide (GB-115) on the behavior of rhesus monkeys in isolation
- Authors: Panchenko A.V.1, Panchenko A.V.1, Pavlova L.E.1, Timina M.F.1, Cherkashina E.V.1, Kolik L.G.2, Seredenin S.B.2
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Affiliations:
- Research Institute of Medical Primatology
- Research Institute of Pharmacology named after. V.V. Zakusova
- Issue: Vol 21, No 6 (2023)
- Pages: 20-26
- Section: Reviews
- URL: https://journals.eco-vector.com/1728-2918/article/view/624950
- DOI: https://doi.org/10.29296/24999490-2023-06-03
- ID: 624950
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Abstract
Introduction. The developed domestic dipeptide retro-analog of cholecystokinin (CCK) tetrapeptide (N-(6-phenylhexanoyl)-glycyltryptophan amide, compound GB-115) with antagonistic properties towards CCK1 receptors has anxiolytic activity, previously shown in preclinical and clinical studies.
Purpose of the study. Evaluation of the anxiolytic effect of GB-115 in tablet dosage form with subchronic oral administration in comparison with phenazepam in laboratory primates.
Methods. The experiment was performed on four male rhesus monkeys (Macaca mulatta) aged 5.7–6.7 years. After a 30-day period of adaptation to the conditions of individual housing, an experiment was performed with GB-115 (0.001 g tablets) and then with phenazepam (0.0005 g tablets). Both drugs were given one at a time (7 days), and then 2 tablets (7 days). Behavior was assessed by observing the object with registration according to the “Yes-No” principle of ethogram elements in the background periods, during the administration of drugs and during their withdrawal. Using enzyme immunoassay, the content of stress response biomarkers: cortisol and dehydroepiandrosterone sulfate (DHEA-S) was determined in blood serum.
Results. GB-115 (0.001 g each) and phenazepam (0.001 g each) reduced the stay of animals in the upper part of the cage compared to the background period, which indicates a decrease in the stress response. GB-115 (0.002 g each) decreased the cortisol/DHEA-S ratio. Phenazepam dose-dependently reduced serum cortisol levels without affecting DHEA-S levels; with the administration of phenazepam (0.001 g), a decrease in the cortisol/DHEA-S ratio was also recorded.
Conclusion. A positive effect of GB-115, when administered subchronically, on the weakening of the emotional stress reaction and restoration of adaptive behavior in rhesus monkeys was revealed, comparable to the effect of phenazepam, which confirms the possibility of using blockade of CCK1 receptors as one of the approaches for the treatment of anxiety disorders.
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About the authors
Alla V. Panchenko
Research Institute of Medical Primatology
Author for correspondence.
Email: shmaliy.a.v@gmail.com
ORCID iD: 0000-0003-1294-751X
Leading researcher, Laboratory of Molecular Biology, Candidate of medical sciences, Assistant Professor
Russian Federation, st. Mira, p. 177, p. Vesele, Adler district, Sochi, Krasnodar region, 354376Andrey V. Panchenko
Research Institute of Medical Primatology
Email: ando_pan@mail.ru
ORCID iD: 0000-0002-5346-7646
Chief Researcher Laboratory of Molecular Biology, Doctor of medical sciences
Russian Federation, st. Mira, p. 177, p. Vesele, Adler district, Sochi, Krasnodar region, 354376Laura E. Pavlova
Research Institute of Medical Primatology
Email: pavlova_laura@mail.ru
ORCID iD: 0000-0002-0638-0986
Researcher Laboratory of Molecular Biology
Russian Federation, st. Mira, p. 177, p. Vesele, Adler district, Sochi, Krasnodar region, 354376Maria F. Timina
Research Institute of Medical Primatology
Email: free_marshmallows@mail.ru
ORCID iD: 0000-0002-1916-238X
Junior researcher Laboratory of Molecular Biology
Russian Federation, st. Mira, p. 177, p. Vesele, Adler district, Sochi, Krasnodar region, 354376Elena V. Cherkashina
Research Institute of Medical Primatology
Email: cherkashina.e78@mail.ru
ORCID iD: 0009-0008-8090-7695
Veterinarian
Russian Federation, st. Mira, p. 177, p. Vesele, Adler district, Sochi, Krasnodar region, 354376Larisa G. Kolik
Research Institute of Pharmacology named after. V.V. Zakusova
Email: lgkolik@mail.ru
ORCID iD: 0000-0002-9847-8058
Chief researcher Laboratory for Pharmacological Regulation, Doctor of biological sciences, Professor of RAS
Russian Federation, st. Baltiyskaya, 8, Moscow, 125315Sergey B. Seredenin
Research Institute of Pharmacology named after. V.V. Zakusova
Email: seredeninpharm@mail.ru
ORCID iD: 0000-0003-4482-9331
Scientific director, Doctor of medical sciences, Professor, Academician of RAS
Russian Federation, st. Baltiyskaya, 8, Moscow, 125315References
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