Патофизиологическая роль системы глюкагоноподобного пептида-1 в регуляции стресс-индуцированных нарушений импульсивного и компульсивного поведения у крыс: ИННОВАЦИОННАЯ ФАРМАКОЛОГИЯ

Николай Сергоевич  Деданишвили; Сарнг Саналович  Пюрвеев; Андрей Андреевич  Лебедев; Андрей Глебович  Васильев; Анна Валентиновна  Васильева; Мария Александровна  Пахомова; Петр Дмитриевич  Шабанов

doi:10.56871/RBR.2026.87.25.007

Pathophysiological role of the glucagon-like peptide-1 system in the regulation of stress-induced impairments of impulsive and compulsive behavior in rats

INNOVATIVE PHARMACOLOGY

Nikolay S. Dedanishvili Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0001-6231-445X
Sarng S. Pyurveev Saint Petersburg State Pediatric Medical University; Institute of Experimental Medicine https://orcid.org/0000-0002-4467-2269
Andrei A. Lebedev Institute of Experimental Medicine https://orcid.org/0000-0003-0297-0425
Andrey G. Vasiliev Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0002-8539-7128
Anna V. Vasilieva Saint Petersburg State Pediatric Medical University https://orcid.org/0009-0008-2356-1552
Mariya A. Pahomova Saint Petersburg State Pediatric Medical University https://orcid.org/0009-0002-4570-8056
Petr D. Shabanov Institute of Experimental Medicine https://orcid.org/0000-0003-1464-1127

Keywords:

glucagon-like peptide-1 (GLP-1) exenatide impulsivity compulsivity stress maternal deprivation rat mesolimbic system глюкагоноподобный пептид-1 (GLP-1) эксенатид импульсивность компульсивность стресс материнская депривация крысa мезолимбическая система

Abstract

Introduction.The glucagon-like peptide-1 (GLP-1) system plays an important role not only in the regulation of energy metabolism but also in the control of motivational and reward-related behavior. Recent studies have demonstrated that GLP-1 receptor agonists can modulate the activity of mesolimbic brain structures involved in the development of impulsivity and addictive behavior. However, the effect of GLP-1 system activation on stress-induced disturbances of self-control remains insufficiently studied.Aim.To determine the role of the glucagon-like peptide-1 (GLP-1) system in regulating impulsive and compulsive behavior that develops in rats following early-life stress (temporary maternal separation), and to evaluate the effects of pharmacological activation of GLP-1 receptors on behavioral manifestations associated with impaired self-control and emotional regulation.Materials and Methods.Experiments were carried out on Wistar rats exposed to maternal separation during the postnatal period. Impulsivity was assessed using a modified decision-making test with different reinforcement probabilities (analogous to the Iowa Gambling Task), and compulsivity was evaluated using the marble burying test. The GLP-1 receptor agonist exenatide (Byetta®, Astra Zeneca, UK) was administered subcutaneously at a dose of 10 µg/kg daily for 7 days. Statistical analysis was performed using Student’s t-test; data are presented as mean±SEM, and differences were considered significant atp<0.05.Results.Administration of the GLP-1 agonist resulted in a significant reduction in impulsive behavior, expressed as a decreased frequency of risky arm choices in the probabilistic reinforcement task compared to saline-treated rats (p<0.05). At the same time, no significant effect was observed on compulsive behavior in the marble burying test.Conclusions.Activation of GLP-1 receptors by exenatide exerts a selective anti-impulsive effect while maintaining the level of compulsive responses, indicating a modulatory role of the GLP-1 system primarily in the regulation of the impulsive component of behavior. The obtained results support the potential of GLP-1 receptor agonists as pharmacological agents for correcting stress-induced impairments of self-control and addiction-related behavioral disorders.

Author Biographies

Nikolay S. Dedanishvili, Saint Petersburg State Pediatric Medical University

Graduate Student, Department of Biological Chemistry

Sarng S. Pyurveev, Saint Petersburg State Pediatric Medical University; Institute of Experimental Medicine

Cand. Sci. (Med.), Junior Research, Department of Neuropharmacology named after S.V. Anichkov, Institute of Experimental Medicine; Associate Professor
of the Department of Pathological Physiology with a Course of Immunopathology, Saint Petersburg State Pediatric Medical University

Andrei A. Lebedev, Institute of Experimental Medicine

Dr. Sci. (Biol.), Professor, Head of the Laboratory of General Pharmacology,
Department of Neuropharmacology named after S.V. Anichkov

Andrey G. Vasiliev, Saint Petersburg State Pediatric Medical University

Dr. Sci. (Med.), Professor, Head of the Department of Pathological Physiology with a Course of Immunopathology

Anna V. Vasilieva, Saint Petersburg State Pediatric Medical University

Assistant Professor, Department of Pathological Physiology with the Course of Immunopathology

Mariya A. Pahomova, Saint Petersburg State Pediatric Medical University

Senior Researcher, Research Center

Petr D. Shabanov, Institute of Experimental Medicine

Dr. Sci. (Med.), Professor and Head, Department of Neuropharmacology named after S.V. Anichkov

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Pathophysiological role of the glucagon-like peptide-1 system in the regulation of stress-induced impairments of impulsive and compulsive behavior in rats: INNOVATIVE PHARMACOLOGY. (2026). Russian Biomedical Research, 11(1), 67-76. https://doi.org/10.56871/RBR.2026.87.25.007

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