Psychopharmacology and Addiction BiologyPsychopharmacology and Addiction BiologyПсихофармакология и биологическая наркология1606-81812070-5670Eco-Vector63586810.17816/phbn635868Biological narcologyБиологическая наркологияResearch ArticleEffects of the new ghrelin receptor antagonist agrelax on compulsive overeating induced by acute and chronic stress in ratsВлияние нового антагониста грелиновых рецепторов агрелакса на компульсивное переедание, вызванное острым и хроническим стрессами у крысhttps://orcid.org/0000-0002-2957-226X4153-1270NadbitovaNatalia D.НадбитоваНаталия Дмитриевна
Russian Federation

MD, Cand. Sci. (Medicine)

кандидат мед. наук

natali_805@mail.ruhttps://orcid.org/0000-0002-4467-22695915-9767PyurveevSarng S.ПюрвеевСарнг Саналович
Russian Federation
dr.purveev@gmail.comNetesaMariya A.НетесаМария Александровна
Russian Federation
saintula@gmail.comhttps://orcid.org/0000-0003-0297-04254998-5204LebedevAndrei A.ЛебедевАндрей Андреевич
Russian Federation

Dr. Sci. (Biology), Professor

доктор биол. наук, профессор

aalebedev-iem@rambler.ruhttps://orcid.org/0000-0003-1464-11278974-7477ShabanovPetr D.ШабановПетр Дмитриевич
Russian Federation

MD, Dr. Sci. (Medicine), professor

доктор мед. наук, профессор

pdshabanov@mail.ruInstitute of Experimental MedicineИнститут экспериментальной медициныInstitute of Experimental MedicineИнститут экспериментальной медициныSaint Petersburg State Pediatric Medical UniversityСанкт-Петербургский государственный педиатрический медицинский университет261020241531992100909202409092024Copyright ©; 2024, Eco-VectorCopyright ©; 2024, Эко-Вектор2024Eco-VectorЭко-Векторhttps://creativecommons.org/licenses/by-nc-nd/4.0https://journals.eco-vector.com/1606-8181/article/view/635868

BACKGROUND: Intense and prolonged stress can be detrimental to both psychological and physical health. Stress often leads to the development or worsening of compulsive overeating. Compulsive overeating is characterized by recurrent episodes of consuming large amounts of food, accompanied by a sense of loss of control.

AIM: To study the effects of the ghrelin receptor antagonist Agrelax on compulsive overeating induced by acute and chronic stress in rats.

MATERIALS AND METHODS: The study involved 150 male and 15 female Wistar rats. To simulate compulsive overeating, the animals received a high-calorie mixture based on chocolate paste three times a week, while maintaining free access to standard food and water. Compulsive behavior was assessed using the marble burying test. Different groups of animals were exposed to various stressors, including maternal deprivation, limb electrical stimulation, partial sensory and complete social isolation, and acute vital stress. Agrelax, a ghrelin receptor antagonist, was administered intranasally at a dose of 1 μg/μL, 10 μL in each nostril, for 7 days.

RESULTS: Compulsive behavior was evaluated using the marble burying test. The experimental group on a high-calorie diet buried significantly more marbles than the control group (p < 0.01). After a 7-day course of Agrelax, the number of buried marbles significantly decreased, reaching the control group values (p < 0.05). A model of compulsive overeating in rats was successfully developed by providing high-calorie food three times a week. After a 7-day course of Agrelax, the consumption of high-calorie food significantly decreased (p < 0.05). Limb electrical stimulation significantly increased the consumption of high-calorie food (p < 0.05). After a 7-day course of Agrelax, the consumption of high-calorie food significantly decreased (p < 0.01). Maternal deprivation stress significantly increased the consumption of high-calorie food (p < 0.001). After a 7-day course of Agrelax, the consumption of high-calorie food decreased, reaching the control group values. In animals raised under partial sensory and complete social isolation, Agrelax did not significantly reduce the consumption of high-calorie food. In animals subjected to acute vital stress, Agrelax did not reduce the consumption of high-calorie food.

CONCLUSIONS: The data obtained suggest new ways for synthesizing peptide pharmacological agents based on ghrelin and its antagonists to treat eating disorders.

Актуальность. Сильные и продолжительные стрессы могут быть опасны как для психологического, так и физического здоровья человека. Нередко стресс приводит к развитию или усугублению компульсивного переедания. Компульсивное переедание характеризуется рецидивирующими эпизодами поедания большого объема пищи с чувством утраты контроля над собой.

Цель — изучить действие антагониста рецепторов грелина агрелакса на компульсивное переедание, вызванное острым и хроническим стрессами у крыс.

Материалы и методы. В исследовании было задействовано 150 самцов и 15 самок крыс линии Вистар. Для моделирования компульсивного переедания животные получали высококалорийную смесь на основе шоколадной пасты 3 раза в неделю при сохранении свободного доступа к стандартному корму и воде. Компульсивность в поведении оценивали с помощью теста закапывания шариков. В качестве стрессорных воздействий для разных групп животных использовали материнскую депривацию, электростимуляцию конечностей, частичную сенсорную и полную внутривидовую изоляцию, острый витальный стресс. Антагонист рецепторов грелина агрелакс вводили интраназально 1 мкг / 1 мкл, по 10 мкл в каждую ноздрю в течение 7 дней.

Результаты. Проведена оценка компульсивного поведения в тесте закапывания шариков. Опытная группа животных, получающая высококалорийное питание, закапывала достоверно большее количество шариков, чем контрольная (p < 0,01). После 7-дневного курса агрелакса количество закопанных шариков значимо снижалось, доходя до значений контрольной группы (p < 0,05). Отработана методика компульсивного переедания у крыс при выдаче высококалорийной пищи 3 раза в нед. После 7-дневного курса агрелакса потребление высококалорийной пищи достоверно снижалось (p < 0,05). Воздействие электростимуляции конечностей значимо увеличивало количество съедаемой высококалорийной пищи (p < 0,05). После 7-дневного курса агрелакса потребление высококалорийной пищи достоверно снижалось (p < 0,01). Стресс материнской депривации значимо увеличивал потребление высококалорийной пищи (p < 0,001). После 7-дневного курса агрелакса, потребление высококалорийной пищи снижалось до показателей контрольной группы. У животных, выращенных в условиях частичной сенсорной и полной внутривидовой изоляции, применение агрелакса не дало выраженного эффекта снижения количества потребляемой высококалорийной пищи. У животных, перенесших острое витальное воздействие, применение агрелакса не снижало количества потребляемой высококалорийной пищи.

Выводы. Полученные данные предполагают новые пути синтеза фармакологических средств пептидной природы на основе грелина и его антагонистов для коррекции пищевой зависимости.

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