Probability Of Using The Behavioral Responses Of Danio Rerio In Assessment Of Dose-Dependent Effects Of Phenazepam

Lebedev, Viktor A.; Лебедев, А. А.; Bychkov, Eugenii R.; Shabanov, Petr Dmitriyevich

doi:10.29296/2618723x-2018-01-02

Cited by 5 publications

(2 citation statements)

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“…Рыбку помещали сначала в мерный стакан водоизмещением 200 мл с растворенным фармакологическим веществом (или водой) на 5 мин, затем в предстартовый аквариум с водой (10 × 10 × 10 см) на 5 мин и далее в просмотровый аквариум на 6 мин, где регистрировали двигательную активность за опыт (длина трека рыбки), число переходов в верхнюю и нижнюю половины аквариума и время нахождения в них. Автоматически регистрировали число и время паттернов «фризинг» (обездвиживание, или «примерзание») за опыт, которые обычно наблюдаются при стрессе новизны и отражают уровень тревожности животного [37]. Поведение регистрировали автоматически с помощью системы NoldusEthoVision XT7, которая позволяет просмотреть видеотреки рыбки.…”

Section: тест стресса новизныunclassified

Study of the effects of kisspeptin analogs on the behavior of Danio rerio

Goltz¹,

Lebedev

2023

Rev Clin Pharm Drug Ther

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The neuropeptide kisspeptin is currently most widely known as a regulator of mammalian sexual behavior. For pharmacological analysis, mammalian Kiss1 kisspeptin analogues were used, Clone (USA): KS4, KS5, KS6, KS7, KS8, KS9 and Kiss 10. 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 was dissolved in water and used 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. This paper compares kisspeptines with anxiolytics using phenazepam as an example in the novelty test. It was shown that in response to the novelty of being placed in the viewing tank, fish responded by diving to the bottom, increasing freesing, and decreasing the number of movements to the upper half of the tank. Fish residence time in the lower part of the tank after administration of phenazepepam decreased, especially when used at a dose of 0.5 and 1 mg/liter. Kisspeptin analogues decreased the indices characterizing the anxious state of the fish. Against the background of Kiss1 kisspeptin analogues, the average fish path length differed significantly in contrast to the effects of phenazepam. KS 4 at a dose of 0.1 mg/L showed a 1.4-fold decrease in the number of freesing, 1.4-fold decrease in the freesing time and 1.4-fold decrease in the trajectory length. The number of transitions to the upper part of the tank increased 1.5 times. The dose of 0.01 mg/l decreased the number of freesing by 1.5 times, freesing time by 1.5 times, trajectory length by 3 times. KS 5 at a dose of 0.1 mg/L decreased the number of freesings by a factor of 1.6, the freesing time by a factor of 1.6, and the trajectory length by a factor of 1.17. The number of transitions to the upper part of the tank increased 1.5 times. The dose of 0.01 mg/l decreased the number of freesing by 3 times, freesing time by 2.8 times, trajectory length by 2.8 times. KS 6 at a dose of 0.1 mg/l decreased the number of freesings by 2.7 times, the freesing time by 2 times, and the trajectory length by 2.5 times. The number of transitions to the upper part of the aquarium increased 2.5 times. The dose of 0, 01 mg/ml decreased the number of freesing by 2.6 times, freesing time by 2.6 times, trajectory length by 1.7 times. KS 7 at a dose of 0.1 mg/L decreased the number of freesing by a factor of 1.7, freesing time by a factor of 1.4, and trajectory length by a factor of 1.3. The number of movements to the top of the aquarium increased 1.6-fold. The dose of 0.01 mg/l decreased the number of freesing by 1.7 times, freesing time by 1.4 times, trajectory length by 1.6 times. KS8 at a dose of 0.1 mg/L decreased the number of freesings by 1.6 times, the freesing time by 1.7 times, and the trajectory length by 1.6 times. The dose of 0.01 mg/l decreased the number of freesing by 2.3 times, the freesing time by 2.2 times, and the trajectory length by 1.8 times. KS9 at a dose of 0.1 mg/l decreased the number of freesing by 2.2 times, the freesing time by 2.2 times, and the trajectory length by 1.2 times. The dose of 0.01 mg/L reduced the number of freesings by 1.5 times, the freesing time by 1.5 times, and the trajectory length by 1.6 times. In Kiss 10 at a dose of 0.1 mg/L, there was a 1.6-fold decrease in the number of frizzings, a 1.5-fold decrease in freezing time, and a 1.4-fold decrease in trajectory length. There was a 2.7-fold increase in the transitions to the upper part of the aquarium. The dose of 0.01 mg/l decreased the number of freesing by 1.7 times, freesing time by 1.6 times, trajectory length by 1.3 times. We observed a 1.3-fold increase in the number of trajectories. Summarizing the obtained indicators, we came to the conclusion that kisspeptin analogues were not inferior in their effect to the effects obtained after taking the tranquilizer phenazepam. Among mammalian kisspeptin analogues, KS6 at a dose of 0.1 mg/L showed the best performance. It is concluded that mammalian Kiss1 kisspeptin analogues and Kiss 10 reduce anxiety-phobic reactions to novelty in Danio rerio. At the same time, the effects of the studied kisspeptin analogues are lower than those of phenazepam. Kisspeptin is involved not only in the modulation of 5-HT-dependent behavior in Danio rerio, but also in the GABA-ergic system as benzodiazepine-type tranquilizers. The results 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.

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Section: тест стресса новизныunclassified

Study of the effects of kisspeptin analogs on the behavior of Danio rerio

Goltz¹,

Lebedev

2023

Rev Clin Pharm Drug Ther

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“…[D-Lys3]-GHRP-6 is a peptide fragment of substance P, exhibiting the properties of an antagonist of GHSR 1A receptors (Shabanov et al 2020). Phenazepam belongs to the group of benzodiazepine anxiolytics (Shabanov et al 2017, Lebedev et al 2018. CRF and [D-Lys3]-GHRP-6 are received from Tocris (UK).…”

Section: Pharmacological Substancesmentioning

confidence: 99%

In search of new brain biomarkers of stress

Shabanov¹,

Blazhenko²,

Devyashin³

et al. 2021

RRP

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The aim: of the study was to investigate the level of ghrelin in various brain structures during a stress response in Zebrafish to a predator, to evaluate this indicator as a potential biomarker of stress, and the effect of a benzodiazepine tranquilizer (phenazepam) on stress-induced changes Materials and methods: The object of the study was Zebrafish, or Danio rerio wild type, which was subjected to stress by exposure to a predator Hypsophrys nicaraguensis from the cichlid family. In the tail tissue, the level of cortisol was determined, in the brain – the level of total (acylated and non-acylated) ghrelin by the method of enzyme-linked immunosorbent assay. The benzodiazepine anxiolytic phenazepam (1 mg/L), a ghrelin antagonist [D-Lys3]-GHRP-6 (0.333 mg/l) and corticotropin-releasing hormone (CRF; 0.4 mg/L) were used as the pharmacological agents. Results and discussion: Exposure to a predator, just as administering CRF, more than doubled the level of cortisol in the tail tissue. [D-Lys3]-GHRP-6 and phenazepam prevented an increase in a tissue cortisol level. Simultaneously, in the medulla oblongata and cerebellum, the phylogenetically most ancient structures, rather than in the forebrain (telencephalon) or in the midbrain (corpora bigemia), the level of ghrelin was recorded about 500 pg/g of total protein. In response to exposure to a predator, the level of ghrelin increased in the forebrain and midbrain to nanogram concentrations and moderately decreased in the cerebellum. The effect was prevented by phenazepam and [D-Lys3]-GHRP-6. Conclusion: Increases in ghrelin in the brain in response to stressful situations can be seen as a functional brain biomarker of stress, along with increased levels of tissue cortisol levels. Both of these effects are prevented by both the ghrelin antagonist and the benzodiazepine tranquilizer. The mechanism of action of the tranquilizer is a functional antagonism between the GABAergic system of the brain and the ghrelin system.

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Experimental assessment of the neurotoxicity of antitumor drugs in Danio rerio fish

Zairkhanova,

Virina,

Nogaeva

et al. 2024

HERALD of North-Western State Medical University named after I.

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BACKGROUND: Neurotoxicity is one of the specific complications of antitumor therapy, which is a serious problem both during the therapy itself and when creating models for its study. Behavioral tests on Danio rerio fish act as an excellent model for creating neurotoxicity and allow to evaluate it in the shortest possible time. AIM: To evaluate the neurotoxic properties of the anticancer drugs doxorubicin and oxaliplatin on Danio rerio (zebrafish) fish through behavioral tests and their evaluation using a program for manual processing of animal behavior. MATERIALS AND METHODS: 45 adult Danio rerio fish were used in the study. Three groups were formed: control group (n = 15), experimental group No. 1 (n = 15) — doxorubicin, experimental group No. 2 (n = 15) — oxaliplatin. A specific dose of the drug was selected for each experimental group. After completing the course of drugs, behavioral tests were conducted, which were recorded on a video camera and processed in the RealTimer application. All tests were repeated three days later to detect reversible neurotoxicity. RESULTS: As a result of the effects of the antitumor drugs doxorubicin and oxaliplatin on Danio rerio fish, neurotoxic abnormalities were detected, which were noticed during behavioral tests: “Social interaction”, “Social preference” and “Aggression”. In the case of doxorubicin, the fish showed severe irritability and high activity, while the fish treated with oxaliplatin showed inhibition and frequent cases of freezing. CONCLUSIONS: During the experiment, a new model was developed and tested to study the neurotoxicity of antitumor drugs on Danio rerio (zebrafish) fish. In addition to confirming the neurotoxicity of antitumor drugs, reversible nephrotoxicity of oxaliplatin was obtained. The study showed the possibility of using the program to evaluate test results in Danio rerio (zebrafish) fish.

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Probability Of Using The Behavioral Responses Of Danio Rerio In Assessment Of Dose-Dependent Effects Of Phenazepam

Cited by 5 publications

References 0 publications

Study of the effects of kisspeptin analogs on the behavior of<i> Danio rerio</I>

Study of the effects of kisspeptin analogs on the behavior of<i> Danio rerio</I>

In search of new brain biomarkers of stress

Experimental assessment of the neurotoxicity of antitumor drugs in <i>Danio rerio</i> fish

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