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.
Abstract. The effect of benzodiazepine anxiolytic diazepam in Danio rerio was investigated. 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 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 diazepam exposure (administration), the fish was not only in the lower, but also in the upper part of the novel tank. A pharmacological analysis of diazepam effect in Danio rerio showed that in a certain dose range of 110 mg/l anxiolytic reduces (in comparison with the control group of fish) the number and time of freezing, increases the number of movements in the upper half of the tank and the swimming time in upper part of the tank. Diazepam causes a disinhibition of motor activity at doses of 1 and 5 mg/l, which may be explained by the effect of small doses of tranquilizers on presynaptic GABA-A autoreceptors. Diazepam 20 mg/l has a depriving effect. Conclusion. Diazepam acts in a higher dose range (110 mg/l) than phenazepam (0.11 mg/l) in Danio rerio. At the same time, diazepam is characterized by a domed dose-dependent effect, in contrast to the action of phenazepam. The prospect of using Danio rerio as an animal model in behavioral pharmacology is not inferior to studies in rodents.
Introduction. A study of the effects of coumarins has not received widespread use in medicine, largely due to the lack of optimal dosage forms, the creation of which is complicated by their poor solubility in water. Currently, studies are underway on the synthesis of macromolecules, combining various structural fragments, which will lead to increased biological activity of the synthesized coumarin derivatives compared to natural coumarins. The aim of this work was to study the central effect of new coumarin-based compounds: IEM-2262, IEM-2263, IEM-2266, IEM-2267 on emotional and research behavior in rats. Methods. Studies have been carried out using battery of tests that are commonly used to study emotional and exploratory behavior: an open field test and an elevated plus maze in rats. The neuroprotector mexidol (200 mg/kg i.p., Farmasoft, Russia) was used as a reference substance. Results. Coumarins (1050 mg/kg ip) have been shown to have a mild psychotropic, predominantly anti-anxiety and sedative effect. 7-Alkoxycoumarins (IEM-2262 and IEM-2266) and 4-aminocoumarins (IEM-2263 and IEM-2267) have different sensitivity in the open field compared with the effects in the elevated plus maze. Anxiolytic properties appeared in the elevated plus maze after the administration of 4-aminocoumarins (IEM-2263 and IEM-2267). The number of defecation boluses in the open field decreased as a result of the administration of 7-alkoxycoumarins (IEM-2262), which was associated not only with fear of novelty, but to a greater extent with anti-stress action. Thus, the new coumarin derivatives have mild tranquilizing and anti-stress effects and can be used in the future for post-traumatic stress disorders with panic attacks.
BACKGROUND: Previously has been shown that fish kisspeptin 1 (Kiss1) acts on the brains serotonin system to reduce anxiety-phobic reactions in Danio rerio. The kissspeptin gene (kiss1) of teleost fish is also a conservative orthologue of the kissspeptin gene (KISS1/Kiss1) of mammals. AIM: In this work we investigated the possible anxiolytic effect of mammalian kisspeptin analogs Kiss1 in Danio rerio in comparison with antidepressants of the serotonin-type of action. MATERIALS AND METHODS: A novelty test was used: the fish was first placed in a beaker with a dissolved pharmacological substance (or H2O), and then in a viewing tank for 6 min, where the trajectory of movement, the length of the path, the number of movements to the upper part of the tank, the time spent in the lower part of the tank, number and time of the freezing were automatically recorded. RESULTS: It is shown that, in response to the novelty of being placed in a viewing tank, fish react by moving to the bottom, increasing friezing, and reducing the number of movements to the upper half of the tank. Against the background of antidepressants clomipramine, paroxetine or trazodone (0.51 mg per 1 l of water), the fish were not only in the lower, but also in the upper part of the viewing tank. The average path length did not change significantly. The time in the lower part of the tank decreased by more than 2 times compared with the control group of animals and showed a dose-dependent effect. The number of movements to the upper part of the tank per experience increased significantly. Mammalian kisspeptin analogues Cloud Clone (USA) in a dose 0.011 mg per 1 l of water caused a similar patterns of behavior in fish in response to novelty. At the same time, the effects of kisspeptin analogs were lower than those of antidepressants. The most effective dose for the action of the studied kisspeptin analogs was 0.1 mg per 1 l of water. CONCLUSIONS: Thus, mammalian kisspeptin analogs Kiss1 reduce anxiety-phobic responses to novelty in Danio rerio. Data on the unidirectional effects of mammalian kisspeptin analogs and serotonin-type antidepressants support the potential role of Kiss1 in modulating serotonin-dependent behaviours in Danio rerio. The data obtained support the hypothesis that kisspeptin may be involved in the regulation of anxiety-phobic states, apparently to maintain the emotional aspects of reproductive behavior, such as sexual motivation and arousal.
We studied the effect of benzodiazepine anxiolytic phenazepam after the predator presentation to Danio rerio. The test of novelty was used: the fish was placed first in a beaker with a dissolved pharmacological substance (or H2O) 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 were measured. It is shown that, in response to the novelty of tank, the fish are reacted by submerging to the bottom, increasing the frizing, and reducing the number of movements to the upper half of the novel tank. After phenazepam administration, the fish were 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 doses used. The number and time of the frizing, as well as the time spent in the lower part of the novel tank, decreased more than 2 times 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. 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. Predator presentation (Hypsophrys nicaraguensis) caused an increase in the number of freezing (temporary immobilization) and a decrease in the length of the trajectory of movement in the novel tank as compared with the Danio rerio control group. Phenazapam at a dose of 1 mg/l removed the effects of a predator, while exhibiting a typical effect: the number of movements to the upper part of the tank during the experiment significantly increased to 30; the time at the bottom of the tank was halved. It was concluded that the novelty stress test and the test with a predator are highly sensitive for studying anxiety-phobic reactions in Danio rerio.
In our previous work, we suggested that analogues of mammalian kisspeptin Kiss1 reduce anxiety-phobic reactions to novelty in Danio rerio. The most effective dose for the action of the studied analogues of kisspeptin corresponded to 0.1 mg per 1000 ml of water. In this work, it was shown that other analog of mammalian kisspeptin Kiss1 at a dose of 0.1 mg per 1000 ml of water also reduced the anxious behavior of Danio fish. The effect of Kiss 1 and Kiss 2 kisspeptins on the behavior of Danio rerio was also evaluated. In the novel test it was revealed that the number of freezings decreased by 2 times against the background of the introduction of kisspeptin 10, and by 3 times after the introduction of the analogue of kisspepin. An analogue of mammalian kisspeptin reduced the freezing time by 2 times. The length of the trajectory decreased by 2 times under the influence of the mammalian Kiss 1 analogue of kisspeptin. Also, against the background of the action of kisspeptin 10, the number of transitions to the upper part of the tank increased by 2 times. After the introduction of the kisspeptin analogue, the number of transitions to the upper part of the aquarium increased by 3 times. In the predator test, the number and time of freezings decreased by 1.5 times against the background of 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 3 times. After the introduction of kisspeptin 10, the trajectory increased by 2 times, and the time spent in the lower part of the tank decreased by 2 times. Kisspeptins of bony fish also reduced anxiety-phobic reactions in fish, but to a lesser extent. Thus, kisspeptin 10 and an analogue of mammalian kisspeptin in response to the presentation of a predator had more significant effects on anxiety in Danio rerio compared to the action of kisspeptin bony fish Kiss 1 and Kiss 2. It is concluded that bony fish kisspeptins and mammalian kisspeptins can reduce anxiety-phobic reactions in Danio rerio, but mammalian kisspeptins are most effective. Bony fish kisspeptin Kiss 1 has an anxiolytic effect in contrast to Kiss 2, which suggests that it affects the reduction of fear, and Kiss 2 seems to be responsible for social and sexual behavior. The results support the hypothesis that kisspeptins may be involved in the regulation of anxiety-phobic states, apparently to maintain the emotional aspects of reproductive behavior, such as sexual motivation and arousal.
BACKGROUND: Currently, no study has investigated on the role of ghrelin in the reinforcing system and emotional behavior. Previously, we examined the properties of GHSR1A antagonist [D-Lys3]-GHRP-6 to reduce negative emotional states caused by stress. AIM: To study the involvement of a new peptide antagonist of the GHSR1A receptor agrelax in the control of emotionalexploratory behavior and anxiety in rats. MATERIALS AND METHODS: Experiments were performed on 42 male Wistar rats. The behavior of rats was observed; agrelax 1 g/mL (or water) with a volume of 20 L (10 l in each nostril) was administered intranasally. A battery of behavioral tests was used: an elevated plus maze, an open field, a marble test, an intruderresident test, and an anxiety-phobic state assessment (FS). RESULTS: In the elevated plus maze test, the time spent in the light arm and the number of hangings from the open arm increased in the test animals compared with animals that did not receive the drug (p 0.05). After the administration of agrelax, the number of balloons buried and the number of elevations supported by the wall of the chamber in the marble test decreased compared with that in animals that did not receive the drug (p 0.05). In the open field, agrelax-infected rats showed a decrease in the number of sniffs (p 0.01). In the FS test after the agrelax administration, the time of descent from the platform decreased compared with the control (p 0.05). In the intruderresident test, individual behavior (p 0.01) and protective behavior (p 0.05) decreased after agrelax administration. CONCLUSION: A new peptide antagonist of the GHSR1A receptor agrelax is involved in the control of emotionalexploratory behavior in rats. Agrelax reduced anxiety levels and exploratory activity. The results provide grounds for the development of new approaches to the treatment of phobic spectrum disorders using drugs that modulate ghrelin regulation.
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