An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish

2020 ◽  
Vol 34 (12) ◽  
pp. 1449-1456 ◽  
Author(s):  
Ana CVV Giacomini ◽  
Barbara W Bueno ◽  
Leticia Marcon ◽  
Naiara Scolari ◽  
Rafael Genario ◽  
...  
Keyword(s):  
Acetylcholinesterase Inhibitor ◽  
Model Organism ◽  
Acetylcholinesterase Activity ◽  
Acetylcholinesterase Inhibition ◽  
Whole Body ◽  
The Novel ◽  
Adult Zebrafish ◽  
Tank Test ◽  
Cortisol Levels ◽  
Brain Acetylcholinesterase

Background: A potent acetylcholinesterase inhibitor, donepezil is a cognitive enhancer clinically used to treat neurodegenerative diseases. However, its complete pharmacological profile beyond cognition remains unclear. The zebrafish ( Danio rerio) is rapidly becoming a powerful novel model organism in neuroscience and central nervous system drug screening. Aim: Here, we characterize the effects of 24-h donepezil administration on anxiety-like behavioral and endocrine responses in adult zebrafish. Methods: We evaluated zebrafish anxiety-like behaviors in the novel tank, the light-dark and the shoaling tests, paralleled by assessing brain acetylcholinesterase activity and whole-body cortisol levels. Results: Overall, donepezil dose-dependently decreased zebrafish locomotor activity in the novel tank test and reduced time in light in the light-dark test, likely representing hypolocomotion and anxiety-like behaviors. Donepezil predictably decreased brain acetylcholinesterase activity, also increasing whole-body cortisol levels, thus further linking acetylcholinesterase inhibition to anxiety-like behavioral and endocrine responses. Conclusion: Collectively, these findings suggest negative modulation of zebrafish affective behavior by donepezil, support the key role of cholinergic mechanisms in behavioral regulation in zebrafish, and reinforce the growing utility of zebrafish models for studying complex behavioral processess and their neuroendocrine and neurochemical regulation.

scholarly journals Acute net stress of young adult zebrafish (Danio rerio) is not sufficient to increase anxiety-like behavior and whole-body cortisol

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7469 ◽  
Author(s):  
Amy Aponte ◽  
Maureen L. Petrunich-Rutherford
Keyword(s):  
Animal Model ◽  
Young Adult ◽  
Danio Rerio ◽  
Preference Test ◽  
Whole Body ◽  
The Novel ◽  
Adult Zebrafish ◽  
Handling Stress ◽  
Tank Test ◽  
Acute Stressor

In recent years, the zebrafish (Danio rerio) has become a popular model to study the mechanisms of physiological and behavioral effects of stress, due to the similarity in neural structures and biochemical pathways between zebrafish and mammals. Previous research in this vertebrate animal model has demonstrated an increase in whole-body cortisol resulting from an acute (30-second) net handling stress, but it remains unclear whether such a stressor will concomitantly increase anxiety-like behavior. In addition, as the previous study examined the effects of this acute stressor in adult zebrafish after a brief period of isolation, it is unclear whether this stressor would be effective in eliciting cortisol increases in younger aged subjects without isolation. In the current study, young adult zebrafish (approximately 90 days post-fertilization) were briefly exposed to a net handling stressor and were subsequently subjected to either the novel tank test or the light/dark preference test. The novel tank test was used to measure exploration and habituation in response to a novel environment, and the light/dark preference test was used to measure locomotor activity and scototaxis behavior. All subjects were sacrificed 15 minutes post-stressor and were analyzed for whole-body levels of cortisol. Contrary to expectations, there was no effect of acute net handling on cortisol levels. Similarly, acute net handling did not significantly induce anxiety-like behavior during the novel tank test or the light/dark preference test. Our findings demonstrate that there are possible developmental differences in response to an acute net handling stress, as we did not observe alterations in hormonal or behavioral measures of anxiety in young adult zebrafish. Alternatively, if zebrafish are not isolated before the stressor, they may be more resilient to a brief acute stressor. These results suggest the need for a different or more intense acute stressor in order further explore neuroendocrine mechanisms and anxiety-like behavior at this developmental stage in the zebrafish animal model.

scholarly journals NOS-2 Participates in the Behavioral Effects of Ethanol Withdrawal in Zebrafish

2020 ◽  
Author(s):  
Suianny Nayara da Silva Chaves ◽  
Bruna Patrícia Dutra Costa ◽  
Gabriela Cristini Vidal Gomes ◽  
Monica Lima-Maximino ◽  
Eduardo Pacheco Rico ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ethanol Withdrawal ◽  
Mechanistic Study ◽  
The Novel ◽  
Adult Zebrafish ◽  
Ethanol Abuse ◽  
Tank Test ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase ◽  
Neurobehavioral Effects

Nitric oxide has been implicated in symptoms of ethanol withdrawal in animal models. Zebrafish have been used as models to study neurobehavioral effects of ethanol (EtOH) withdrawal, but the mechanisms associated with these effects are not yet clear. Adult zebrafish were treated with 1% EtOH for 20 min per day for 8 days, injected with the nitric oxide synthase 2 (NOS-2) inhibitor aminoguanidine (50 mg/kg), and allowed to experience withdrawal (WD) in their hometanks for 7 days. EtOH WD increased anxiety-like behavior in the novel tank test, an effect that was blocked by aminoguanidine. EtOH WD also increased brain levels of nitrite, an effect that was partially blocked by aminoguanidine. These results underline a novel mechanism by which NOS-2 controls anxiety-like responses to ethanol withdrawal, with implications for the mechanistic study of symptoms associated with chronic ethanol abuse.

Calocybe indicia extract modifies GABA and Serotonin levels to Alleviate anxiety in experimental adult Zebrafish models

2021 ◽  
pp. 4789-4794
Author(s):  
Sarah Andrea Wilson ◽  
Anushree Nagaraj ◽  
Lalitha Vaidyanathan
Keyword(s):  
Biochemical Parameters ◽  
Anxiolytic Effect ◽  
The Novel ◽  
Adult Zebrafish ◽  
Tissue Weight ◽  
Mao A ◽  
Before And After ◽  
Tank Test ◽  
Gaba Content ◽  
Calocybe Indica

Zebrafish (Danio rerio) was used as a model to study anxiety due to its physiological homology to humans. The pathophysiology of anxiety, even though still unclear, has been extensively studied in Zebrafish. Anxiety was induced by withdrawal after exposure to 0.5% ethanol, which proved to be anxiogenic, validated through the novel tank test. The light/dark test revealed that exposure to 0.5% ethanol had anxiolytic effects. The milky mushroom, Calocybe indica was used to treat anxiety since its anti-hypertensive effects have already been reported. Biochemical parameters such as GABA and MAO (A&B) were measured before and after treatment with different concentrations of C. indica and standard anxiolytic drug, Fluoxetine to compare and confirm the anxiolytic effect. The GABA content was found to be 119.9±1.99 mmoles/g tissue weight after treatment with 50 µg C. indica which was comparable to the normal group values (100±4.12). MAO (A&B) activity decreased which in turn increased serotonin levels with 25µg of C. indica. 25µg and 100µg concentration of the extract of C. indica was found to be optimum in reducing the level of anxiety.

scholarly journals Indication of Electromagnetic Field Exposure via RBF-SVM Using Time-Series Features of Zebrafish Locomotion

Sensors ◽  
2020 ◽  
Vol 20 (17) ◽  
pp. 4818
Author(s):  
Yaqing He ◽  
Kim Fung Tsang ◽  
Richard Yuen-Chong Kong ◽  
Yuk-Tak Chow
Keyword(s):  
Time Series ◽  
Environmental Parameters ◽  
Empirical Method ◽  
Support Vector ◽  
The Novel ◽  
Adult Zebrafish ◽  
Field Exposure ◽  
Magnetic Exposure ◽  
Tank Test ◽  
The Impact

This paper introduces a novel model based on support vector machine with radial basis function kernel (RBF-SVM) using time-series features of zebrafish (Danio rerio) locomotion exposed to different electromagnetic fields (EMFs) to indicate the corresponding EMF exposure. A group of 14 adult zebrafish was randomly divided into two groups, 7 in each group; the fish of each group have the novel tank test under a sham or real magnetic exposure of 6.78 MHz and about 1 A/m. Their locomotion in the tests was videotaped to convert into the x, y coordinate time-series of the trajectories for reforming time-series matrices according to different time-series lengths. The time-series features of zebrafish locomotion were calculated by the comparative time-series analyzing framework highly comparative time-series analysis (HCTSA), and a limited number of the time-series features that were most relevant to the EMF exposure conditions were selected using the minimum redundancy maximum relevance (mRMR) algorithm for RBF-SVM classification training. Before this, ambient environmental parameters (AEPs) had little effect on the locomotion performance of zebrafish processed by the empirical method, which had been quantitatively verified by regression using another group of 14 adult zebrafish. The results have demonstrated that the purposed model is capable of accurately indicating different EMF exposures. All classification accuracies can be 100%, and the classification precision of several classifiers based on specific parameters and feature sets with specific dimensions can reach higher than 95%. The speculative reason for this result is that the specified EMF has affected the zebrafish neural aspect, which is then reflected in their behaviors. The outcomes of this study have provided a new indication model for EMF exposures and provided a reference for the investigation of the impact of EMF exposure.

Influence of pH on the Acute Lethality of Fenitrothion, 2,4-D, and Aminocarb and Some pH-Altered Sublethal Effects of Aminocarb on Rainbow Trout (Salmo gairdneri)

1988 ◽  
Vol 45 (2) ◽  
pp. 287-293 ◽  
Author(s):  
K. G. Doe ◽  
W. R. Ernst ◽  
W. R. Parker ◽  
G. R. J. Julien ◽  
P. A. Hennigar
Keyword(s):  
Rainbow Trout ◽  
Sublethal Effects ◽  
Acetylcholinesterase Activity ◽  
Whole Body ◽  
Toxicity Tests ◽  
Salmo Gairdneri ◽  
Control Range ◽  
Decreasing Ph ◽  
Influence Of Ph ◽  
Brain Acetylcholinesterase

Three pesticides, fenitrothion, 2,4-D, and aminocarb, were tested in static 96-h acute lethal toxicity tests using fingerling rainbow trout (Salmo gairdneri) at pH 4.6, 5.6, 6.9, and 8.5. The toxicity of aminocarb, a base, increased significantly with increasing pH. Conversely, the toxicity of the acidic pesticide 2,4-D increased with decreasing pH. The toxicity of the neutral pesticide fenitrothion did not change significantly with changing pH. Subsequent tests were performed on trout fingerlings with aminocarb to determine the effect of two exposure pH's on brain acetylcholinesterase activity and whole-body aminocarb residue. Brain acetylcholinesterase was found to be inversely proportional to whole-body aminocarb content of fish. In fish exposed at pH 4.6, brain acetylcholinesterase was maximally depressed at 6 h, after which it recovered to within the control range. Whole-body aminocarb concentrations rose to a maximum within 6 h and subsequently declined to low levels. In fish exposed at pH 8.2, brain acetylcholinesterase dropped below the control range by 1 h and remained low until all fish died by 72 h. A maximum whole-body aminocarb concentration was reached within 1 h and remained elevated until the fish died. Several explanations for the observed results are presented.

scholarly journals NOS-2 Participates in the Behavioral Effects of Ethanol Withdrawal in Zebrafish

2020 ◽  
Author(s):  
Suianny Nayara da Silva Chaves ◽  
Bruna Patrícia Dutra Costa ◽  
Gabriela Cristini Vidal Gomes ◽  
Monica Lima-Maximino ◽  
Eduardo Pacheco Rico ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ethanol Withdrawal ◽  
Mechanistic Study ◽  
The Novel ◽  
Adult Zebrafish ◽  
Ethanol Abuse ◽  
Tank Test ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase ◽  
Neurobehavioral Effects

Nitric oxide has been implicated in symptoms of ethanol withdrawal in animal models. Zebrafish have been used as models to study neurobehavioral effects of ethanol (EtOH) withdrawal, but the mechanisms associated with these effects are not yet clear. Adult zebrafish were treated with 1% EtOH for 20 min per day for 8 days, injected with the nitric oxide synthase 2 (NOS-2) inhibitor aminoguanidine (50 mg/kg), and allowed to experience withdrawal (WD) in their hometanks for 7 days. EtOH WD increased anxiety-like behavior in the novel tank test, an effect that was blocked by aminoguanidine. EtOH WD also increased brain levels of nitrite, an effect that was partially blocked by aminoguanidine. These results underline a novel mechanism by which NOS-2 controls anxiety-like responses to ethanol withdrawal, with implications for the mechanistic study of symptoms associated with chronic ethanol abuse.

scholarly journals NOS-2 Participates in the Behavioral Effects of Ethanol Withdrawal in Zebrafish

2019 ◽  
Author(s):  
Suianny Nayara da Silva Chaves ◽  
Bruna Patrícia Dutra Costa ◽  
Gabriela Cristini Vidal Gomes ◽  
Monica Lima-Maximino ◽  
Eduardo Pacheco Rico ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ethanol Withdrawal ◽  
Mechanistic Study ◽  
The Novel ◽  
Adult Zebrafish ◽  
Ethanol Abuse ◽  
Tank Test ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase ◽  
Neurobehavioral Effects

Nitric oxide has been implicated in symptoms of ethanol withdrawal in animal models. Zebrafish have been used as models to study neurobehavioral effects of ethanol (EtOH) withdrawal, but the mechanisms associated with these effects are not yet clear. Adult zebrafish were treated with 1% EtOH for 20 min per day for 8 days, injected with the nitric oxide synthase 2 (NOS-2) inhibitor aminoguanidine (50 mg/kg), and allowed to experience withdrawal (WD) in their hometanks for 7 days. EtOH WD increased anxiety-like behavior in the novel tank test, an effect that was blocked by aminoguanidine. EtOH WD also increased brain levels of nitrite, an effect that was partially blocked by aminoguanidine. These results underline a novel mechanism by which NOS-2 controls anxiety-like responses to ethanol withdrawal, with implications for the mechanistic study of symptoms associated with chronic ethanol abuse.

scholarly journals Anxiety-like behavior and whole-body cortisol responses to components of energy drinks in zebrafish (Danio rerio)

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7546 ◽  
Author(s):  
Alia O. Alia ◽  
Maureen L. Petrunich-Rutherford
Keyword(s):  
Danio Rerio ◽  
Stress Responses ◽  
Physiological Stress ◽  
Energy Drinks ◽  
Energy Drink ◽  
Whole Body ◽  
Control Group ◽  
The Novel ◽  
Neuroendocrine Responses ◽  
Cortisol Levels

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.

scholarly journals Adult zebrafish anaesthesia: a study of efficacy and behavioural recovery of different anaesthetics

2021 ◽  
Author(s):  
Sara Jorge ◽  
Jorge M Ferreira ◽  
I Anna S Olsson ◽  
Ana M Valentim
Keyword(s):  
Fish Behaviour ◽  
The Novel ◽  
Clove Oil ◽  
Adult Zebrafish ◽  
Long Term Effects ◽  
Fish Welfare ◽  
Equilibrium Response ◽  
Tank Test ◽  
Fish Activity

AbstractThe use of proper anaesthesia in zebrafish research is essential to ensure fish welfare and data reliability. However, anaesthesia long-term side effects remain poorly understood. The purpose of this study was to assess anaesthesia quality and recovery in adult zebrafish using different anaesthetic protocols and to determine possible long-term effects on the fish activity and anxiety-like behaviours after anaesthesia.Mixed sex adult AB zebrafish were randomly assigned to 5 different groups (control, 175mg/L MS222, 45 mg/L clove oil, 2 mg/L etomidate and 5mg/L propofol combined with 150mg/L lidocaine) and placed in the respective anaesthetic bath. Time to lose the equilibrium, response to touch and to tail pinch stimuli, and recovery after anaesthesia administration were evaluated. In addition, after stopping anaesthesia, respiratory rate, activity and anxiety-like behaviours in the novel tank test were studied.Overall, all protocols proved to be adequate for zebrafish anaesthesia research as they showed full recovery at 1h, and only etomidate had minor effects on fish behaviour in the novel tank, a validated test for anxiety.

scholarly journals (-)-Phenserine Ameliorates Contusion Volume, Neuroinflammation, and Behavioral Impairments Induced by Traumatic Brain Injury in Mice

2019 ◽  
Vol 28 (9-10) ◽  
pp. 1183-1196 ◽  
Author(s):  
Shih-Chang Hsueh ◽  
Daniela Lecca ◽  
Nigel H. Greig ◽  
Jia-Yi Wang ◽  
Warren Selman ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Motor Coordination ◽  
Acetylcholinesterase Inhibitor ◽  
Acetylcholinesterase Activity ◽  
Phase Iii ◽  
Acetylcholinesterase Inhibition ◽  
Motor Asymmetry ◽  
Post Injury ◽  
Behavioral Impairments

Traumatic brain injury (TBI), a major cause of mortality and morbidity, affects 10 million people worldwide, with limited treatment options. We have previously shown that (-)-phenserine (Phen), an acetylcholinesterase inhibitor originally designed and tested in clinical phase III trials for Alzheimer’s disease, can reduce neurodegeneration after TBI and reduce cognitive impairments induced by mild TBI. In this study, we used a mouse model of moderate to severe TBI by controlled cortical impact to assess the effects of Phen on post-trauma histochemical and behavioral changes. Animals were treated with Phen (2.5 mg/kg, IP, BID) for 5 days started on the day of injury and the effects were evaluated by behavioral and histological examinations at 1 and 2 weeks after injury. Phen significantly attenuated TBI-induced contusion volume, enlargement of the lateral ventricle, and behavioral impairments in motor asymmetry, sensorimotor functions, motor coordination, and balance functions. The morphology of microglia was shifted to an active from a resting form after TBI, and Phen dramatically reduced the ratio of activated to resting microglia, suggesting that Phen also mitigates neuroinflammation after TBI. While Phen has potent anti-acetylcholinesterase activity, its (+) isomer Posiphen shares many neuroprotective properties but is almost completely devoid of anti-acetylcholinesterase activity. We evaluated Posiphen at a similar dose to Phen and found similar mitigation in lateral ventricular size increase, motor asymmetry, motor coordination, and balance function, suggesting the improvement of these histological and behavioral tests by Phen treatment occur via pathways other than anti-acetylcholinesterase inhibition. However, the reduction of lesion size and improvement of sensorimotor function by Posiphen were much smaller than with equivalent doses of Phen. Taken together, these results show that post-injury treatment with Phen over 5 days significantly ameliorates severity of TBI. These data suggest a potential development of this compound for clinical use in TBI therapy.

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