BACKGROUND: Factors that may trigger episodes of binge eating include mental and physical stress, dietary restrictions of high-calorie foods. In a rodent model it has been shown that intermittent consumption of high-calorie foods causes binge eating regardless of body weight gain. AIM: To investigate the effect of a novel ghrelin receptor antagonist Agrelax on binge eating in in adult rats after maternal deprivation in early ontogeny. MATERIALS AND METHODS: Animals were weaned for 180 min from day 2 to day 12 after birth; males 90100 days of age were used in the experiments. In the development of binge eating, animals received a high-carbohydrate diet (Nutella paste based chocolate mixture) for 1 h every day or every third day for 1.5 months. Fifteen minutes before feeding, the chocolate paste was placed within 5 cm of reach with visual contact. Agrelax, a novel ghrelin receptor antagonist, was administered intranasally 1g/1l, 20l for 7 days. RESULTS: Maternal deprivation induced bindge eating of high-calorie foods in adult rats. When chocolate was given 3 times a week, its consumption increased (p 0.001) in the maternal deprivation group relative to the control group. After a course of administration of agrelax, chocolate consumption did not differ significantly from that in the control group. The daily consumption of standard food did not differ relative to the control group both before and after the course of agrelax administration. When chocolate was given daily, the maternal deprivation rats did not develop food addiction. At the same time agrelax did not induce a change in chocolate consumption relative to the control group. CONCLUSIONS: The findings suggest new ways to synthesize pharmacological agents of peptide nature based on ghrelin and its antagonists for correction of food addiction caused by psychogenic stresses in ontogenesis.

Background. Мesocortical and nigrostriatal dopaminergic systems are highly sensitive to stressful events. One of the most adequate models of acute psychogenic stress in animals is the death of a partner upon presentation of a predator. Aim. To study the content of dopamine (DA), serotonin and their metabolites: dioxyphenylacetic (DOPAC), homovanillic and 5-hydroxyindoleacetic (5-HIAA) acids in the prefrontal cortex, striatum, and ventral tegmental area in rats on days 3, 7, and 14 after the acute psychogenic stress of the death of a partner upon presentation of a predator. Materials and methods. 28 male Wistar rats were studied. Acute single psychotraumatic situation was used. A group of rats was placed in a tiger python terrarium. One animal died as a result of its nutritional needs, the rest of the rats experienced the death of a partner. The content of monoamines in the brain structures was carried out by high performance liquid chromatography with electrochemical detection. Results. Changes in the content of monoamines in the prefrontal cortex, striatum, and ventral tegmental area were found on the 7 and 14 days after the presentation of the predator. In the ventral tegmental area on the 7 day, there was an increase in the DOPAC/DA ratio and an increase in the serotonin metabolite 5-HIAA, which reflects an increase in the activity of dopamine and serotonin. In the prefrontal cortex on the 14 day, the DOPAС content and the DOPAС/DA index decreased. The 5-HIAA content in the prefrontal cortex and the 5-HIAA/5-HT value also significantly decreased. Conclusions. Changes in the metabolism of monoamines after presentation of a predator develop gradually: increase of the dopamine and serotonin activity in the ventral tegmental area was noted on the 7 day after presentation of the predator, decrease in their activity in the striatum and prefrontal cortex only on the 14 day, reflecting the development of depressive states and post-traumatic stress disorder.

Введение. Целью настоящего исследования было изучение интраназального введения антагониста рецептора грелина [D-Lys-3]-GHRP-6 на импульсивность и компульсивность в модели игровой зависимости у взрослых крыс после материнской депривации в раннем онтогенезе. Материалы и методы. Крысята подвергались материнской (МД) ежедневно в течение 3 часов с 2 по 12 послеродовой день. Далее половозрелые крысы обучались в тесте вероятности и величины подкрепления IOWA Gambling task трехрукавном лабиринте в течение 21 дня. Каждая побежка в 1 рукав лабиринта с режимом подкрепления FR1 подкреплялась двумя пищевыми таблетками. Каждая вторая побежка во 2 рукав лабиринта с режимом подкрепления FR2 подкреплялась тремя пищевыми таблетками; каждая третья побежка в 3 рукав с режимом подкрепления FR3 подкреплялась четырьмя пищевыми таблетками. Соответственно, половина заходов в рукав 2 и 2/3 заходов в рукав 3 оставались без подкрепления. Для оценки компульсивного поведения животных также тестировали в тесте закапывания шариков. Крысу помещали в клетку с опилками и стеклянными шариками на 30 минут, после чего считали количество шариков, покрытых опилками более чем на 2/3. Результаты и обсуждение. В группе МД количество заходов в 3 рукав увеличилось в 1,5 раза, что свидетельствует о выборе большего подкрепления при низкой вероятности его получения. Количество заходов в рукав 1 уменьшилось по сравнению с контрольной группой. Интраназальное введение селективного антагониста рецептора GHSR1A [D-Lys (3)]-GHRP-6 (1 мг/мл) животным МД приводило к достоверному (p<0,01) увеличению количества посещений 1 рукава. Кроме того, наблюдалась тенденция к уменьшению количества зарытых шариков у крыс, получавших [D-Lys (3)]-GHRP-6. Заключение. Таким образом, работа показывает, что хронический стресс МД приводит к поведенческой стратегии у животных, направленной на получение более значительного пищевого подкрепления, но с низкой вероятностью его достижения, что связано с увеличением импульсивного компонента игровой зависимости. МД также вызывает увеличение количества закопанных шариков в тесте с закапывания шариков, что связано с увеличением компульсивного компонента игровой зависимости. Интраназальное введение антагониста GHS-R1a [D-Lys (3)]-GHRP-6 крысам МД значительно снижает повышенную импульсивную активность в тесте вероятности и величины подкрепления. Полученные данные открывают возможность создания лекарств, мишенью которых могут быть рецепторы грелина. Интраназальный метод введения пептидных веществ, использованный в работе, подтверждает возможность использования этого метода введения.

BACKGROUND: Gambling addiction (gambling) involves frequently repeated episodes of gambling that are detrimental to social, professional, material, and family values. Gambling addiction is often combined with posttraumatic stress disorder. AIM: This study aimed to examine the effect of predator presentation stress on the manifestations of gambling addiction in an animal model in a test of probability and magnitude of reinforcement in the Iowa gambling task and monoamine metabolism in the prefrontal cortex of rats. MATERIALS AND METHODS: Rats were trained in a test of probability and magnitude of reinforcement in the Iowa gambling task in a 3-beam maze. Each run in arm 1 of the maze was reinforced with one sunflower seed, each second run in arm 2 with two seeds, and each third run in arm 3 with three seeds. Correspondingly, half of the runs in arm 2 and 2/3 of the runs in arm 3 were left unreinforced. After training, the animals were placed in a terrarium with a tiger python, one of which was victimized for its food requirements. On day 14 after predator presentation, dopamine and serotonin metabolism in the prefrontal cortex was determined using high-performance liquid chromatography with electrochemical detection. RESULTS: The levels of the dopamine metabolite dioxyphenylacetic acid and the ratio of dioxyphenylacetic acid to dopamine in the prefrontal cortex decreased. The levels of serotonin, its metabolite 5-hydroxyindoleacetic acid, and the ratio of 5-hydroxyindoleacetic acid to serotonin in the prefrontal cortex were also decreased in rats after exposure to a predator. Moreover, predator presentation induced significant behavioral changes in rats, increasing impulsivity in making choices in a test of probability and magnitude of reinforcement in the Iowa gambling task. The acute vital stress of predator presentation increased the number of escapes to arm 3 of the maze, suggesting that the animals exhibited more risky behavior when choosing reinforcements of different strengths and probability. CONCLUSIONS: The animal model showed that the depletion of the dopaminergic and serotoninergic systems of the prefrontal cortex underlies pathological gambling addiction and inadequate decision-making caused by posttraumatic stress disorder.

BACKGROUND: Exposure to acute or chronic stress contributes to the occurrence of various disorders of the central nervous system, psycho-emotional sphere, as well as increases the risks of development of various forms of addiction. AIM: The aim of the study is analyze the influence of maternal deprivation on voluntary alcohol consumption in adolescents and to determine the degree of the signs of compulsive behavior in experimental animals. MATERIALS AND METHODS: Thirty male Wistar rats were taken in the research. A maternal deprivation model was carried out from day 2 to day 12 of the postnatal period (MD). Compulsivity (compulsive tendency) was evaluated in the ball burial test. Voluntary alcoholization with 10% ethyl alcohol solution in a two-bottle test was employed. Level of progesterone in blood plasma was determined by enzyme- immune analyses. RESULTS: Changes in the level of progesterone in blood plasma in MD and control group of animals were detected. In the test of two bottles 10% of ethanol solution presented on days 2 and 3, statistically significant differences in consumption were determined in contrast to the control group. In the test of balloon diapering, MD group of animals showed a statistically proved significant increase in compulsiveness both before the beginning of voluntary alcoholization and on day 3 from the start. CONCLUSIONS: The increase in compulsivity and voluntary ethanol consumption was significantly higher in the MD group, that is comparable to the increased level in blood plasma progesterone samples.

In our previous work, we suggested that analogs of mammalian kisspeptin Kiss1 reduce anxiety and phobic reactions novel in Danio rerio. The most effective dose for the action of the studied analogs of kisspeptin corresponded to 0.1 mg per 1000 mL of water. In this study, other analogs of mammalian Kiss1 at a dose of 0.1 mg per 1000 mL of water also reduced the anxious behavior of Danio fish. The effect of Kiss1 and Kiss2 kisspeptins on the behavior of Danio rerio was also evaluated. In the novel test, the number of freezing decreased by two times with the introduction of kisspeptin 10 and by three times after the introduction of the kisspeptin analog. An analog of mammalian kisspeptin reduced the freezing time by two times. The length of the trajectory decreased by two times under the influence of the mammalian Kiss1 kisspeptin analog. With the action of kisspeptin 10, the number of transitions to the upper part of the tank increased by two times. After the introduction of the kisspeptin analog, the number of transitions to the upper part of the aquarium increased by three times. In the predator test, the number and time of freezing decreased by 1.5 times with the action of mammalian kisspeptins. The length of the trajectory after the introduction of kisspeptin bony fish and kisspeptin 10 mammals increased. The length of the trajectory after the introduction of Kiss1 increased by 1.5 times. The length of the trajectory after the introduction of Kiss2 increased by three times. After the introduction of kisspeptin 10, the trajectory increased by two times, and the time spent in the lower part of the tank decreased by two times. Kisspeptins of bony fish also reduced the anxiety and phobic reactions in fish, but to a lesser extent. Thus, kisspeptin 10 and an analog of mammalian kisspeptin in response to the presentation of a predator had more significant effects on anxiety in Danio rerio compared with the action of kisspeptin bony fish Kiss1 and Kiss2. Thus, bony fish kisspeptins and mammalian kisspeptins can reduce anxiety and phobic reactions in Danio rerio; however, mammalian kisspeptins are the most effective. Bony fish kisspeptin Kiss1 has an anxiolytic effect in contrast to Kiss2, which suggests that it affects fear reduction, and Kiss2 appears to be responsible for social and sexual behavior. The results support the hypothesis that kisspeptins may be involved in the regulation of anxiety and phobic states, apparently to maintain the emotional aspects of reproductive behavior, such as sexual motivation and arousal.