scholarly journals 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

2017 ◽  
Vol 15 (3) ◽  
pp. 57-63 ◽  
Author(s):  
Petr D. Shabanov ◽  
Viktor A. Lebedev ◽  
Andrei A. Lebedev ◽  
Eugenii R. Bychkov

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.


2021 ◽  
Vol 19 (1) ◽  
pp. 71-78
Author(s):  
Andrei A. Lebedev ◽  
Aleksandr S. Devyashin ◽  
Aleksandra A. Blazhenko ◽  
Sergei V. Kazakov ◽  
Viktor A. Lebedev ◽  
...  

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.



2020 ◽  
Vol 18 (1) ◽  
pp. 43-49
Author(s):  
Aleksandr S. Devyashin ◽  
Aleksandra A. Blazhenko ◽  
Viktor A. Lebedev ◽  
Andrei A. Lebedev ◽  
Eugenii R. Bychkov ◽  
...  

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.



2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joshua Szaszkiewicz ◽  
Shannon Leigh ◽  
Trevor J. Hamilton

AbstractTerpenes are fragrant aromatic compounds produced by a variety of plants, most notably cannabis and hops. With increasing legalization of cannabis there is a need to better understand the behavioural effects of terpenes and ultimately their therapeutic value. Our study investigated the dose-dependent impact of three terpenes (limonene 0.25, 0.5, 0.75%; β-myrcene 0.001, 0.01, 0.1%; and 0.0001, 0.001, 0.00125% linalool) on zebrafish (Danio rerio) behaviour when exposed both acutely and repeatedly over a 7-day period. Anxiety-like behaviour, boldness, and locomotion were assessed using the open field test and the novel object approach test. In the acute dosing experiment, limonene and β-myrcene exposed groups demonstrated a significant decrease in locomotion, a decrease in anxiety-like behaviour, and an increase in boldness, while linalool treatment groups demonstrated only minor alterations in locomotion. Moreover, repeated exposure to limonene (0.39%) or β-myrcene (0.0083%) for a seven day period did not result in any significant behavioural effects. In conclusion, our study provides support for an anxiolytic and sedative effect in zebrafish in response to acute limonene and β-myrcene exposure that is no longer present after one week of repeated exposure.



2020 ◽  
Vol 18 (4) ◽  
pp. 44-54
Author(s):  
O. V. Grebenyuk ◽  
V. M. Alifirova ◽  
M. V. Svetlik ◽  
N. G. Kataeva ◽  
V. N. Vasilyev

The aim of the study was to investigate vegetative maintenance of the activity and state of systemic hemodynamics in patients with a first time, non-traumatic epileptic seizure during a tilt table test (TTT).Materials and methods. TTT was performed in 42 patients with absence of seizures and 78 patients having experienced unprovoked seizures. A control group included 70 patients with non-epileptic seizures with transient loss of consciousness (TLC), defined as syncope. The control group included 38 people without episodes of loss of consciousness in their medical history. The parameters of hemodynamics and heart rate variability (HRV) were investigated at all stages of the test.Results. In patients with absence of seizures, initial sympathicotonia was recorded along with a decrease in ergotropic activation in orthostasis. In patients with unprovoked seizures, a hypersympathicotonic response to the orthostatic test was detected in combination with impaired vagal overshoot in the clinostatic phase of the test. In patients with TLC, evidence of vegetative insufficiency in the vertical position was identified, with the indicators going back to the background values in the horizontal position.Conclusion. The revealed features of vegetative regulation in patients with absence of seizures and unprovoked seizures will allow to differentiate the mechanism of the first-time epileptic seizure more accurately. 



2017 ◽  
Vol 64 (2) ◽  
Author(s):  
C. Akbulut ◽  
B. Ozturk ◽  
A. Uzun ◽  
N. D. Yon

Tribenuron methyl is a herbicide that is used to control annual and perennial dicots in cereals and fallow land. Pesticides can access aquatic ecosystems via groundwater and affect water quality and aquatic life. Our study evaluated histopathological effects of tribenuron methyl on ovary of the zebrafish Danio rerio (Hamilton, 1822). Ovary of the fishes in control group not exposed to the herbicide showed normal histological architecture. In the fishes exposed to tribenuron methyl, vacuolisation, edema and dysmorphism were recorded. Significant decrease in the number of primary and mature oocytes as well as dose dependent increase in the number of atretic oocytes were recorded in fishes exposed to tribenuron methyl.



2021 ◽  
Author(s):  
Joshua Szaszkiewicz ◽  
Shannon Leigh ◽  
Trevor J. Hamilton

Abstract Terpenes are fragrant aromatic compounds produced by a variety of plants, most notably cannabis and hops. With increasing legalization of recreational and medicinal cannabis there is growing interest to better understand the behavioural effects of terpenes and ultimately their therapeutic value. Our study investigated the dose-dependent impact of three terpenes (limonene 0.25, 0.5, 0.75%; β-myrcene 0.001, 0.01, 0.1%; and 0.0001, 0.001, 0.00125% linalool) on zebrafish (Danio rerio) behaviour when exposed both acutely and repeatedly over a 7-day period. Anxiety-like behaviour, boldness, and locomotion were assessed using the open field test and the novel object approach test. In the acute dosing experiment, limonene and β-myrcene treatment groups demonstrated a significant decrease in locomotion, a decrease in anxiety-like behaviour, and an increase in boldness, while linalool treatment groups had minor alterations in locomotion. Moreover, chronic exposure to limonene (0.39%) or β-myrcene (0.0083%) did not result in any significant behavioural effects, suggesting that anxiety-like behaviour, locomotion, and boldness were not impacted at these levels. In conclusion, our study provides support for an anxiolytic and sedative effect in zebrafish in response to acute limonene, β-myrcene, and linalool exposure.



PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7546 ◽  
Author(s):  
Alia O. Alia ◽  
Maureen L. Petrunich-Rutherford

The current study investigated the independent and combined effects of caffeine and taurine on anxiety-like behavior and neuroendocrine responses in adult zebrafish (Danio rerio). Caffeine (1,3,7-trimethylpurine-2,6-dione), the world’s most commonly used psychoactive drug, acts as an adenosine receptor blocker and a mild central nervous system stimulant. However, excessive use of caffeine is associated with heightened anxiety levels. Taurine (2-aminoethanesulfonic acid), a semi-essential amino acid synthesized within the human brain, has been hypothesized to play a role in regulating anxiolytic behavior. Caffeine and taurine are two common additives in energy drinks and are often found in high concentrations in these beverages. However, few studies have investigated the interaction of these two chemicals with regards to anxiety measures. A suitable vertebrate to examine anxiety-like behavior and physiological stress responses is the zebrafish, which has shown promise due to substantial physiological and genetic homology with humans. Anxiety-like behavior in zebrafish can be determined by analyzing habituation to novelty when fish are placed into a novel tank and scototaxis (light avoidance) behavior in the light-dark test. Stress-related neuroendocrine responses can be measured in zebrafish by analyzing whole-body cortisol levels. The goal of this study was to determine if exposure to caffeine, taurine, or a combination of the two compounds altered anxiety-like behavior and whole-body cortisol levels in zebrafish relative to control. Zebrafish were individually exposed to either caffeine (100 mg/L), taurine (400 mg/L), or both for 15 min. Zebrafish in the control group were handled in the same manner but were only exposed to system tank water. After treatment, fish were transferred to the novel tank test or the light-dark test. Behavior was tracked for the first 6 min in the novel tank and 15 min in the light-tark test. Fifteen min after introduction to the behavioral task, fish were euthanized for the analysis of whole-body cortisol levels. The results demonstrate that caffeine treatment decreased the amount of exploration in the top of the novel tank and increased scototaxis behavior in the light-dark test, which supports the established anxiogenic effect of acute exposure to caffeine. Taurine alone did not alter basal levels of anxiety-like behavioral responses nor ameliorated the anxiogenic effects of caffeine on behavior when the two compounds were administered concurrently. None of the drug treatments altered basal levels of whole-body cortisol. The current results of this study suggest that, at least at this dose and time of exposure, taurine does not mitigate the anxiety-producing effects of caffeine when administered in combination, such as with energy drink consumption.



PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6407 ◽  
Author(s):  
Maureen L. Petrunich-Rutherford

Exposure to selective serotonin reuptake inhibitors (SSRIs) during development may elicit long-term neuroadaptive changes that could alter the basal regulation of stress-associated physiological and behavioral processes later in life. Currently, the effects of juvenile fluoxetine exposure in rodent models appear to be dependent on the developmental window targeted as well as the duration of drug exposure. The zebrafish (Danio rerio) model is rapidly becoming a useful tool in pharmacological research and can be used to help elucidate some of the long-term effects of fluoxetine exposure prior to sexual maturation on neuroendocrine and behavioral stress markers. In the current study, juvenile zebrafish were chronically exposed to fluoxetine hydrochloride (0 or 100 μg/L) for 14 days (31–44 days post-fertilization (dpf)), then were left untreated until young adulthood. Starting at 90 dpf, basal neuroendocrine stress and behavioral responses of zebrafish were assessed. Cortisol was extracted from the young adult zebrafish body (trunk) and quantified via enzyme-linked immunosorbent assay (ELISA). Anxiety-like behaviors were assessed in response to introduction to the novel tank test. It was expected that juvenile exposure to fluoxetine would (1) reduce basal cortisol levels and (2) elicit anxiolytic effects in the novel tank test in adulthood. However, fluoxetine exposure during the juvenile period was not associated with alterations in basal levels of cortisol nor were there any significant changes in anxiety-like behavior in the young adult zebrafish. Thus, in zebrafish, it does not appear that SSRI exposure during the juvenile period has a long-term adverse or maladaptive impact on the basal expression of cortisol and anxiety-like behavior in adulthood. Further studies are needed to determine if SSRI exposure during this developmental window influences neuroendocrine and behavioral responses to acute stress.



2021 ◽  
Vol 5 (1) ◽  
pp. 472-476
Author(s):  
A. M. Salim ◽  
A. B. Dauda ◽  
M. A. Yusuf

This study examined the behavioral changes induced by butachlor to the juveniles of Clarias gariepinus. The experiment consists of five treatments (0.6, 0.7, 0.8, 0.9 and 1.0 mg/l) and a control. Ten fishes were allotted in each test tank in duplicates. Observations on behavioral responses were made at 0, 12, 24, 48, 72 and 96 hours post-exposure. The opercular movement and tail fin beat rates were observed as counts per minute using a stopwatch. The behavioral patterns of the fish in the control group were normal, whereas in the exposed groups the fish tend to lose equilibrium and swim erratically with vigorous jerky movements. At the 12th and 24th hours the fish in the exposed groups showed hyper-active movement, but became hypoactive at the 48th hour. The mean values of the tail fin beat of the exposed groups were significantly higher (p<0.05) than that of the control at the 12th hour. At the 24th and 48th hour post-exposure the exposed groups showed significant (p<0.05) time-dependent decrease compared to the control. The tail fin beat became significantly higher (P<0.05) in the control group from 72nd hours onward. The decrease of tail fin beats at the 72nd and 96th hours were dose-dependent similar observations were also recorded in the opercular ventilation. At the 12th hour the opercular ventilation of the exposed fish was significantly higher (p<0.05) than the control whereas at the 24th and 48th hours, the opercular ventilation of the exposed groups showed a significant decrease (p<0.05) compared to the control.



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