Introduction: The purpose of this work was to prove that the reaction of food self-deprivation in “fed up” rats is a suitable model for studying the emotional overeating in the experiment. Methods: The self-deprivation reaction, i.e. self-isolation of an animal from food during electrical self-stimulation of the brain, was studied in animals with food deprivation. To reproduce the self-stimulation of the lateral hypothalamus, the male Wistar rats were trained to press a pedal in a Skinner box. After training, the rats received food deprivation, then a feeder was placed in the Skinner box, and a conditioned food reflex was developed in rats within 5 days. Results and discussion: The food self-deprivation reaction was observed in the ”satiated” rats with a current intensity of 10% and above the threshold for self-stimulation. Hungry animals pressed the pedal for hypothalamic self-stimula­tion and took no notice of the feeding trough. Sulpiride, a dopamine D2 antagonist (5 and 20 mg/kg i.p.), administered to the “satiated” rats decreased both the eating behavior and self-stimulation in food self-deprivation testing. SB-408124, an orexin A receptor antagonist (0.5 mg/ml, 20 μl intranasally) reduced only the number of pellets eaten, but not the number of pedal presses. Conclusion: The orexin A receptors are preferably involved in emotional eating compared with orexin B (OX2R TCS-OX2-29) and D2 dopamine receptors. Because emotional eating is significantly related to clinical eating disorders, like bulimia and binge eating disorder, it seems promising to use drugs of the orexin system to treat and prevent the issue.

The effect of the orexin A OX1R receptor antagonist SB-408124 of on the compulsive behavior and the anxiety in rats after the presentation of vital stress in a number of behavioral tests: marble test, elevated plus maze, in the open field and in the test “resident intruder”. In the buring marble test, the behavioral components of the obsession(obsessiveand obtrusive thoughts) and compulsions (obtrusive behavior), aimed to reduce anxiety, were modeled. Mental trauma was caused by a stressful effect, the essence of which was the experience of the animals of the circumstances of the death of a partner from the actions of a predator. A group of rats were placed once in the terrarium to a tiger python. After the action of vital mental stress in rats, two connected behavioral phenomena were observed: a high level of anxiety and an increase in the number of buried balls. This was accompanied by a decrease in communicability. Intranasal administration (for 7 days) of orexin A antagonist OX1R receptor SB-408124 after presentation of the vital stress reduced the level of anxiety, and also normalized the communicative activity of animals and the number of buried balls, i.e. compulsive behavior. Thus, the orexin system of the brain is an important component of psychotraumatic mechanism. OX1R antagonists of orexin A receptors can potentially be considered as correctors of obsessive-compulsive disorders on the background of posttraumatic stress disorder (PTSD). Use of intranasal administration of OX1R antagonists of orexin A receptors in the clinic will allow the use of small doses of substances and thereby reduce their possible toxic effects. (For citation: Tissen IYu, Yakushina ND, Lebedev AA, et al. Effect of SB-408124, an orexin A OX1R receptor antagonist, on the compulsive behavior and the level of anxiety after the vital stress in rats. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):34-42. doi: 10.17816/RCF16134-42).

We investigated the role of ghrelin and its receptors in the manifestation of gambling addiction elements in rats exposed to early psychogenic stress. Rearing in conditions of social isolation or maternal deprivation in early ontogeny increased risk behavior and impulsivity in the Iowa Gambling Task test: animals sought more food reinforcement, but with a low probability. Maternal deprivation or rearing in social isolation increased expression of Ghsr in the amygdala and hypothalamus respectively. The level of expression of the gene under study in the prefrontal cortex did not change. It is concluded that early psychogenic stress causes an imbalance in the brain ghrelin regulatory system, which manifests itself in increased of Ghsr level as well as elements of gambling addiction. The scheme of the effect of chronic stress on the hypothalamic ghrelin system and on the extrahypothalamic regulation of ghrelin is presented.

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.

The effect of benzodiazepine anxiolytic phenazepam in Danio rerio was investigated. Previously, Danio rerio showed the effects of other anxiolytics, dia_zepam and chlordiazepoxide. The analysis of the anxiolytic effect of phenazepam in Danio rerio was carried out for the first time. Methods. A stress test on novelty situation was used: a fish was placed first in a beaker with a dissolved pharmacological substance (or water) and then into a novel tank for 6 min, where the trajectory, the path length, the number of movements to the upper part of the novel tank, the number and time of the pattern of freezing for each min of the experiment were measured. Results. In response to the novelty of tank, the fish was shown to react by submerging to the bottom, increasing the freezing, and reducing the number of movements to the upper half of the novel tank. After phenazepam exposure (administration), the fish was not only in the lower, but also in the upper part of the novel tank. The average path length did not change significantly in the range of the doses used. The number and time of the freezing, as well as the time spent in the lower part of the novel tank, 2-fold decreased compared to the control group of animals and showed a dose-dependent effect. The number of movements to the upper part of the novel tank for the experiment increased significantly from 1 in the control to 57 after phenazepam in a dose of 1 mg/l. When analyzing the dynamics of the parameters for each min, it was shown that the time of the fish in the lower part of the novel tank decreased from 3th min of the experiment with the use of phenazepam in a dose of 0.5 mg/l. At the same time, the number of movements of fish to the upper part of the novel tank significantly increased more than 2 times from 3th min of the experiment with the use of phenazepam in a dose of 1 mg/l. Conclusion. The described method to study behavioral responses of Danio rerio on novelty stress is high sensitive in comparison with traditional behavioral methods of studing tranquilizers. The prospect of using Danio rerio as animal model in behavioral pharmacology is significant and does not concede research on rodents.

BACKGROUND: Sexual dysfunction is not a specific symptom of posttraumatic stress disorder (PTSD); however, it is a common clinical complaint. Rodents exposed to a traumatic event exhibit behavioral disturbances in tests designed to measure emotional behavior. In relation to sexual behavior, exposure to acute stress leads to a decrease in the frequency of ejaculation and an increase in latency to first intercourse, first intromission, and ejaculation. Kisspeptin is a neuropeptide that plays important roles in the functioning of the hypothalamic–pituitary–gonadal axis and sexual behavior. AIM: To examine the effects of a single traumatic event caused by a predator on sexual behavior and motivation in male rats and correct them using hormonal and nonhormonal regulators. MATERIALS AND METHODS: We used 60 copulatory-naive male Wistar rats aged 90–100 days weighing 220–230 g, which were divided into six groups of 10 animals each. Animals of group 1 were intact; in the remaining groups, PTSD was modeled by exposure to a predator (tiger python). In the experimental groups, animals received buserelin, kisspeptin-10, and yohimbine. An unattainable reinforcement chamber was used to assess sexual motivation. The free locomotor activity of animals was evaluated in the “open-field” test. The elevated plus maze test was used to assess the effects of stress. Blood and brain samples were collected for testosterone and corticosterone enzyme-linked immunosorbent assay. RESULTS: Acute predator stress, as an animal model of PTSD, significantly reduces several components of sexual motivation in male rats and increases serum corticosterone levels. After chronic stress, both intranasal and systemic administrations of kisspeptin increase sexual motivation in male rats. Buserelin significantly affected testosterone secretion but had slightly affected sexual motivation. Systemic administration of kisspeptin partially restored testosterone production in a rat model of stress disorder. Yohimbine did not affect hormonal levels and had a disruptive effect on sexual motivation in rats. None of the hormonal and nonhormonal regulators used affected corticosterone levels. CONCLUSION:The findings indicate that exposure to predator stress has a greater effect on sexual motivation and the hypothalamic–pituitary–adrenal axis than on sex hormone production. This necessitates searching for new mechanisms underlying the regulation of reproductive behavior and the influence of stress factors on its implementation.