Acute effects of amitriptyline on adult zebrafish: Potential relevance to antidepressant drug screening and modeling human toxidromes

Demin, Konstantin A.; Колесникова, Т. А.; Khatsko, Sergey L.; Meshalkina, Darya A.; Efimova, Evgeniya V.; Morzherin, Yu. Yu.; Kalueff, Allan V.

doi:10.1016/j.ntt.2017.04.002

Cited by 48 publications

(74 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Kellner et al (2016) also observed increased swimming activity in fish exposed to 1.5 µg/L citalopram. This effect has not only been shown in response to citalopram but has also been found for other antidepressants like fluoxetine or amitriptyline, which seem to reduce anxiety and increase the stay of the fish in the upper part of the aquarium (Demin et al, 2017;Henry & Black, 2008;Meshalkina et al, 2018)..…”

Section: Behaviour During Exposurementioning

confidence: 69%

Impact of the antidepressant citalopram on the behaviour of two different life stages of brown trout

Knoll

Köhler

Tisler

et al. 2020

PeerJ

View full text Add to dashboard Cite

Background Over the last two decades, there has been a constant increase in prescription rates of antidepressants. In parallel, neuroactive pharmaceuticals are making their way into aquatic environments at increasing concentrations. Among the antidepressants detected in the environment citalopram, a selective serotonin reuptake inhibitor, is one of the most commonly found. Given citalopram is specifically designed to alter mood and behaviour in humans, there is growing concern it can adversely affect the behaviour on non-target wildlife Methods In our study, brown trout were exposed to citalopram (nominal concentrations: 1, 10, 100, 1000 µg/L) in two different life stages. Larvae were exposed at 7 and 11 °C from the eyed ova stage until 8 weeks post yolk sac consumption, and juvenile brown trout were exposed for 4 weeks at 7 °C. At both stages we measured mortality, weight, length, tissue citalopram concentration, behaviour during exposure and behaviour in a stressfull environment. For brown trout larvae additionally hatching rate and heart rate, and for juvenile brown trout the tissue cortisol concentration were assessed. Results During the exposure, both larvae and juvenile fish exposed to the highest test concentration of citalopram (1 mg/L) had higher swimming activity and spent longer in the upper part of the aquaria compared to control fish, which is an indicator for decreased anxiety. Most probably due to the higher swimming activity during the exposure, the juveniles and larvae exposed to 1 mg/L citalopram showed decreased weight and length. Additionally, in a stressful artificial swimming measurement device, brown trout larvae displayed the anxiolytic effect of the antidepressant by reduced swimming activity during this stress situation, already at concentrations of 100 µg/L citalopram. Chemical analysis of the tissue revealed rising citalopram tissue concentrations with rising exposure concentrations. Tissue concentrations were 10 times higher in juvenile fish compared to brown trout larvae. Fish plasma concentrations were calculated, which exceeded human therapeutic levels for the highest exposure concentration, matching the behavioural results. Developmental parameters like hatching rate and heart rate, as well as mortality and tissue cortisol content were unaffected by the antidepressant. Overall, we could trace the pharmacological mode of action of the antidepressant citalopram in the non-target organism brown trout in two different life stages.

show abstract

Section: Behaviour During Exposurementioning

confidence: 69%

Impact of the antidepressant citalopram on the behaviour of two different life stages of brown trout

Knoll

Köhler

Tisler

et al. 2020

PeerJ

View full text Add to dashboard Cite

show abstract

“…Neurochemical analyses. Brain monoamines are an important factor in stress and affective disorders both clinically and in rodents and zebrafish models 37,68,[117][118][119][120][121] . To study dynamic changes in their levels in stressed zebrafish, the whole-brain concentrations of norepinephrine (NE), serotonin (5-HT), dopamine (DA) and their metabolites 5-HIAA, DOPAC and homovanillic acid (HVA) were assayed using the high-performance liquid chromatography (HPLC), as in 68,[119][120][121] .…”

Section: Chronic Unpredictable Stress (Cus)mentioning

confidence: 99%

“…The sample size was chosen here based on previously published studies on zebrafish stress-related behavior, including own works 48,68,120,121,123 and sample size estimation using the R package pwr2. Briefly, for GZLM1, the effect sizes for two factors were estimated using distance (as one of basic zebrafish endpoints) from 48 (stress effect; effect size = 0.68) and 57 (day effect; effect size = 0.75).…”

Section: Statistical Analyses and Data Handling The Present Study Utmentioning

confidence: 99%

Understanding complex dynamics of behavioral, neurochemical and transcriptomic changes induced by prolonged chronic unpredictable stress in zebrafish

Demin

Lakstygal

Krotova

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Stress-related neuropsychiatric disorders are widespread, debilitating and often treatment-resistant illnesses that represent an urgent unmet biomedical problem. Animal models of these disorders are widely used to study stress pathogenesis. A more recent and historically less utilized model organism, the zebrafish (Danio rerio), is a valuable tool in stress neuroscience research. Utilizing the 5-week chronic unpredictable stress (CUS) model, here we examined brain transcriptomic profiles and complex dynamic behavioral stress responses, as well as neurochemical alterations in adult zebrafish and their correction by chronic antidepressant, fluoxetine, treatment. Overall, CUS induced complex neurochemical and behavioral alterations in zebrafish, including stable anxiety-like behaviors and serotonin metabolism deficits. Chronic fluoxetine (0.1 mg/L for 11 days) rescued most of the observed behavioral and neurochemical responses. Finally, whole-genome brain transcriptomic analyses revealed altered expression of various CNS genes (partially rescued by chronic fluoxetine), including inflammation-, ubiquitin- and arrestin-related genes. Collectively, this supports zebrafish as a valuable translational tool to study stress-related pathogenesis, whose anxiety and serotonergic deficits parallel rodent and clinical studies, and genomic analyses implicate neuroinflammation, structural neuronal remodeling and arrestin/ubiquitin pathways in both stress pathogenesis and its potential therapy.

show abstract

“…At 5-days post-fertilization (dpf), zebrafish larvae show spontaneous swimming and their visual system is fully developed. As many reports suggest that the behavioral responses of zebrafish are similar to those of mammals ( Noyes et al, 2015 ; Demin et al, 2017 ; Kim et al, 2017 ), it seems appropriate to use zebrafish for testing of exercise, learning, and memory in behavioral evaluation.…”

Section: Introductionmentioning

confidence: 99%

Neurobehavioral Effects of Cephalosporins: Assessment of Locomotors Activity, Motor and Sensory Development in Zebrafish

et al. 2018

View full text Add to dashboard Cite

Most third- and fourth-generation cephalosporins, such as cefotaxime, cefmenoxime, cefepime, and cefpirome, contain an aminothiazoyl ring at the C-7 position. Drug impurity, which may be produced either during synthesis or upon degradation, can induce adverse effects. Various reports have indicated that neurotoxicity is a side effect of cephalosporin. In this study, we developed methods for assessing the free-swimming activities and behaviors in zebrafish larvae in response to continuous darkness and stimulation of light-to-dark photoperiod transition by chemical treatments. We also performed transcriptome analysis to identify differentially expressed genes (DEGs). Gene ontology analysis revealed that various processes related to nervous system development were significantly enriched by DEGs. We integrated 16 DEGs with protein–protein interaction networks and identified that neuroactive ligand–receptor interaction [e.g., λ-aminobutyric acid and glutamate receptor, metabotropic 1a (GRM1A)] pathway was regulated by the compounds. Our findings suggested that neurobehavioral effects mainly depend on the mother nucleus structure 7-aminocephalosporanic acid and the substitution at the C-3 position. In addition, gad2, or111-4, or126-3, grm1a, opn8c, or111-5, or113-2, and or118-3 may potentially be utilized as novel biomarkers for this class of cephalosporins, which causes neurotoxicity. This study provides neurological behavior, transcriptome, and docking information that could be used in further investigations of the structures and developmental neurotoxicity relationship of chemicals.

show abstract

Acute effects of amitriptyline on adult zebrafish: Potential relevance to antidepressant drug screening and modeling human toxidromes

Cited by 48 publications

References 64 publications

Impact of the antidepressant citalopram on the behaviour of two different life stages of brown trout

Impact of the antidepressant citalopram on the behaviour of two different life stages of brown trout

Understanding complex dynamics of behavioral, neurochemical and transcriptomic changes induced by prolonged chronic unpredictable stress in zebrafish

Neurobehavioral Effects of Cephalosporins: Assessment of Locomotors Activity, Motor and Sensory Development in Zebrafish

Contact Info

Product

Resources

About