Effect of novelty stress on behavioral responses of Danio rerio and assessment of dose-dependent effects of anxiolytics of benzodiazepine structure with phenazepam as an example

Abstract

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.

In search of new brain biomarkers of stress

“…The stress response, accompanied by an increased level of cortisol in the tissues, is eliminated by both the anxiolytic phenazepam and the peptide antagonist ghrelin [D-Lys3]-GHRP-6. The data obtained confirm the involvement of the ghrelin system in the anxiolytic action of benzodiazepines, mainly due to functional antagonism between the ghrelin system and GABAergic mechanisms mediating the effect of benzodiazepines (Guo et al 2012, Shabanov et al 2017.…”

“…[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).…”

Comparative effects of antidepressants of various pharmacological groups on the behavior of adult Danio rerio

“…На сегодняшний день Danio rerio активно используются во многих направлениях научной деятельности: в качестве индикатора загрязнения водоемов, для оценки токсичности фармакологических препаратов, разработки транспортных лекарственных си-стем, а также в качестве модельного объекта постановки стресса новизны и депрессии [6][7][8]. Учитывая эти данные, можно говорить, что Danio rerio в полной мере могут использоваться в качестве модельного объекта в доклинических исследованиях заболеваний нервной системы [9,10].…”