Abstract— At present, the neuropeptide kisspeptin is most widely known as a regulator of sexual behavior in mammals. For the pharmacological analysis, the analogs of mammalian kisspeptin Kiss1 (Cloud-Clone, United States) were used: KS4, KS5, KS6, KS7, KS8, KS9, KS9, and Kiss10. Kisspeptins were dissolved in aquarium water and applied in two doses: (1) 0.01 mg per 1000 mL of water; (2) 0.1 mg per 1000 mL of water. Phenazepam substance of OAO Novosibkhimfarm (Russia) was used as a comparison preparation. Phenazepam was dissolved in water and applied in three doses: (1) 0.1 mg per 1000 mL of water; (2) 0.5 mg per 1000 mL of water; (3) 1 mg per 1000 mL of water. A comparison of kisspeptins with anxiolytics by the example of phenazepam in a novelty test was done in the work. For this, the fish was initially placed in a measuring cup with a dissolved pharmacological substance (or H2O) and then in a viewing aquarium for 6 min, where the trajectory of movement, path length, number of movements to the upper part of the aquarium, time spent in the lower part of the aquarium, number and time of the “freezing” pattern were automatically registered. The time spent by fish in the lower part of the aquarium after the introduction of phenazepam decreased, especially when used at a dose of 0.5 and 1 mg/L. Kisspeptin analogs decreased the indices characterizing an anxious state of the fish. Against the background of the effect of Kiss1 kisspeptin analogs, the average length of fish path differed significantly (unlike the effects of phenazepam). In KS4 at a dose of 0.1 mg/L, a decrease in the number of freezings by 1.4 times, freezing time by 1.4 times, and trajectory length by 1.4 times was noted as compared with the control. The number of transitions to the upper part of the aquarium increased by 1.5 times. At a dose of 0.01 mg/L, the number of freezings decreased by 1.5 times, freezing time by 1.5 times, and trajectory length by 3 times. In KS5 at a dose of 0.1 mg/L, the number of freezings decreased by 1.6 times, freezing time by 1.6 times, and trajectory length by 1.17 times. The number of transitions to the upper part of the aquarium increased by 1.5 times. At a dose of 0.01 mg/L, the number of freezings decreased by 3 times, freezing time by 2.8 times, and trajectory length by 2.8 times. In KS6 at a dose of 0.1 mg/L, the number of freezings decreased by 2.7 times, freezing time by 2 times, and trajectory length by 2.5 times. The number of transitions to the upper part of the aquarium increased by 2.5 times. At a dose of 0.01 mg/mL the number of freezings decreased by 2.6 times, freezing time by 2.6 times, and trajectory length by 1.7 times. In KS7 at a dose of 0.1 mg/L, the number of freezings decreased by 1.7 times, freezing time by 1.4 times, and trajectory length by 1.3 times. The number of transitions to the upper part of the aquarium increased by 1.6 times. At a dose of 0.01 mg/L, the number of freezings decreased by 1.7 times, freezing time by 1.4 times, and trajectory length by 1.6 times. In KS8 at a dose of 0.1 mg/L, the number of freezings decreased by 1.6 times, freezing time by 1.7 times, and trajectory length by 1.6 times. At a dose of 0.01 mg/L, the number of freezings decreased by 2.3 times, freezing time by 2.2 times, and trajectory length by 1.8 times. In KS9 at a dose of 0.1 mg/L, the number of freezings decreased by 2 times, freezing time by 2 times, and trajectory length by 1.2 times. At a dose of 0.01 mg/L, the number of freezings decreased by 1.5 times, freezing time by 1.5 times, and trajectory length by 1.6 times. In Kiss10 at a dose of 0.1 mg/L, a decrease in the number of freezing by 1.6 times, freezing time by 1.5 times, and trajectory length by 1.4 times was observed. There was an increase in the number of transitions to the upper part of the aquarium by 2.7 times. At a dose of 0.01 mg/L, the number of freezings decreased by 1.7 times, freezing time by 1.6 times, and trajectory length by 1.3 times. An increase in the number of trajectories by 1.3 times was observed. Kisspeptin analogs were not inferior to the effects of phenazepam administration. Among kisspeptin analogs in mammals, the best indices were observed for KS6 at a dose of 0.1 mg/L. It was concluded that mammalian Kiss1 kisspeptin analogs and Kiss10 reduce anxiety–phobic reactions to novelty in Danio rerio. At the same time, the effects of the studied kisspeptin analogs are lower than in phenazepam. Kisspeptin is involved not only in the modulation of 5-HT-dependent behavior in Danio rerio but also in the GABAergic system, as benzodiazepine series tranquilizers. The results of the studies support the hypothesis that kisspeptin can apparently be involved in the regulation of anxiety–phobic states to maintain the emotional aspects of reproductive behavior, such as sexual motivation and arousal.

Study of the Effects of Mammalian Kisspeptin Analogs and Kisspeptin 10 in Danio rerio

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发表日期：

2025年4月1日

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V. A. Golts,
A. A. Lebedev,
A. A. Blazhenko,
V. A. Lebedev,
S. V. Kazakov,
A. A. Bayramov,
P. P. Khokhlov,
E. R. Bychkov,
S. S. Purveev,
P. D. Shabanov

摘要

Abstract—

At present, the neuropeptide kisspeptin is most widely known as a regulator of sexual behavior in mammals. For the pharmacological analysis, the analogs of mammalian kisspeptin Kiss1 (Cloud-Clone, United States) were used: KS4, KS5, KS6, KS7, KS8, KS9, KS9, and Kiss10. Kisspeptins were dissolved in aquarium water and applied in two doses: (1) 0.01 mg per 1000 mL of water; (2) 0.1 mg per 1000 mL of water. Phenazepam substance of OAO Novosibkhimfarm (Russia) was used as a comparison preparation. Phenazepam was dissolved in water and applied in three doses: (1) 0.1 mg per 1000 mL of water; (2) 0.5 mg per 1000 mL of water; (3) 1 mg per 1000 mL of water. A comparison of kisspeptins with anxiolytics by the example of phenazepam in a novelty test was done in the work. For this, the fish was initially placed in a measuring cup with a dissolved pharmacological substance (or H₂O) and then in a viewing aquarium for 6 min, where the trajectory of movement, path length, number of movements to the upper part of the aquarium, time spent in the lower part of the aquarium, number and time of the “freezing” pattern were automatically registered. The time spent by fish in the lower part of the aquarium after the introduction of phenazepam decreased, especially when used at a dose of 0.5 and 1 mg/L. Kisspeptin analogs decreased the indices characterizing an anxious state of the fish. Against the background of the effect of Kiss1 kisspeptin analogs, the average length of fish path differed significantly (unlike the effects of phenazepam). In KS4 at a dose of 0.1 mg/L, a decrease in the number of freezings by 1.4 times, freezing time by 1.4 times, and trajectory length by 1.4 times was noted as compared with the control. The number of transitions to the upper part of the aquarium increased by 1.5 times. At a dose of 0.01 mg/L, the number of freezings decreased by 1.5 times, freezing time by 1.5 times, and trajectory length by 3 times. In KS5 at a dose of 0.1 mg/L, the number of freezings decreased by 1.6 times, freezing time by 1.6 times, and trajectory length by 1.17 times. The number of transitions to the upper part of the aquarium increased by 1.5 times. At a dose of 0.01 mg/L, the number of freezings decreased by 3 times, freezing time by 2.8 times, and trajectory length by 2.8 times. In KS6 at a dose of 0.1 mg/L, the number of freezings decreased by 2.7 times, freezing time by 2 times, and trajectory length by 2.5 times. The number of transitions to the upper part of the aquarium increased by 2.5 times. At a dose of 0.01 mg/mL the number of freezings decreased by 2.6 times, freezing time by 2.6 times, and trajectory length by 1.7 times. In KS7 at a dose of 0.1 mg/L, the number of freezings decreased by 1.7 times, freezing time by 1.4 times, and trajectory length by 1.3 times. The number of transitions to the upper part of the aquarium increased by 1.6 times. At a dose of 0.01 mg/L, the number of freezings decreased by 1.7 times, freezing time by 1.4 times, and trajectory length by 1.6 times. In KS8 at a dose of 0.1 mg/L, the number of freezings decreased by 1.6 times, freezing time by 1.7 times, and trajectory length by 1.6 times. At a dose of 0.01 mg/L, the number of freezings decreased by 2.3 times, freezing time by 2.2 times, and trajectory length by 1.8 times. In KS9 at a dose of 0.1 mg/L, the number of freezings decreased by 2 times, freezing time by 2 times, and trajectory length by 1.2 times. At a dose of 0.01 mg/L, the number of freezings decreased by 1.5 times, freezing time by 1.5 times, and trajectory length by 1.6 times. In Kiss10 at a dose of 0.1 mg/L, a decrease in the number of freezing by 1.6 times, freezing time by 1.5 times, and trajectory length by 1.4 times was observed. There was an increase in the number of transitions to the upper part of the aquarium by 2.7 times. At a dose of 0.01 mg/L, the number of freezings decreased by 1.7 times, freezing time by 1.6 times, and trajectory length by 1.3 times. An increase in the number of trajectories by 1.3 times was observed. Kisspeptin analogs were not inferior to the effects of phenazepam administration. Among kisspeptin analogs in mammals, the best indices were observed for KS6 at a dose of 0.1 mg/L. It was concluded that mammalian Kiss1 kisspeptin analogs and Kiss10 reduce anxiety–phobic reactions to novelty in Danio rerio. At the same time, the effects of the studied kisspeptin analogs are lower than in phenazepam. Kisspeptin is involved not only in the modulation of 5-HT-dependent behavior in Danio rerio but also in the GABAergic system, as benzodiazepine series tranquilizers. The results of the studies support the hypothesis that kisspeptin can apparently be involved in the regulation of anxiety–phobic states to maintain the emotional aspects of reproductive behavior, such as sexual motivation and arousal.