Ketamine induces anxiolytic effects in adult zebrafish: A multivariate statistics approach

Campos, Eduardo Geraldo de; Bruni, Aline Thais; Martinis, Bruno Spinosa De

doi:10.1016/j.bbr.2015.07.017

Cited by 21 publications

(9 citation statements)

References 45 publications

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“…Interestingly, pharmacological studies revealed high correlation with regard to the ability of larval and adult zebrafish to mimic positive SCZ symptoms. For example, ketamine [65,66] and MK-801 (also called dizocilpine) [54, 67] induce a robust increase in locomotion. Moreover, d-amphetamine or D 2 receptor agonists elicit the same locomotor response in adult zebrafish [68,69] as in rodents [70][71][72][73][74].…”

Section: Discussionmentioning

confidence: 99%

Zebrafish Larvae Carrying a Splice Variant Mutation in cacna1d: A New Model for Schizophrenia-Like Behaviours?

et al. 2020

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Persons with certain single nucleotide polymorphisms (SNPs) in the CACNA1D gene (encoding voltage-gated calcium channel subunit alpha 1-D) have increased risk of developing neuropsychiatric disorders such as bipolar, schizophrenia and autism. The molecular consequences of SNPs on gene expression and protein function are not well understood. Thus, the use of animal models to determine genotype-phenotype correlations is critical to understanding disease pathogenesis. Here, we describe the behavioural changes in larval zebrafish carrying an essential splice site mutation (sa17298) in cacna1da. Heterozygous mutation resulted in 50% reduction of splice variants 201 and 202 (haploinsufficiency), while homozygosity increased transcript levels of variant 201 above wild type (WT; gain-of-function, GOF). Due to low homozygote viability, we focused primarily on performing the phenotypic analysis on heterozygotes. Indeed, cacna1dasa17298/WT larvae displayed hyperlocomotion—a behaviour characterised in zebrafish as a surrogate phenotype for epilepsy, anxiety or psychosis-like behaviour. Follow-up tests ruled out anxiety or seizures, however, as neither thigmotaxis defects nor epileptiform-like discharges in larval brains were observed. We therefore focused on testing for potential “psychosis-like” behaviour by assaying cacna1dasa17298/WT larval locomotor activity under constant light, during light-dark transition and in startle response to dark flashes. Furthermore, exposure of larvae to the antipsychotics, risperidone and haloperidol reversed cacna1da-induced hyperactivity to WT levels while valproate decreased but did not reverse hyperactivity. Together, these findings demonstrate that cacna1da haploinsufficiency induces behaviours in larval zebrafish analogous to those observed in rodent models of psychosis. Future studies on homozygous mutants will determine how cacna1d GOF alters behaviour in this context.

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Section: Discussionmentioning

confidence: 99%

Zebrafish Larvae Carrying a Splice Variant Mutation in cacna1d: A New Model for Schizophrenia-Like Behaviours?

et al. 2020

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“…lysergic acid diethylamide (LSD), mescaline and psilocybin] alter zebrafish locomotion, shoaling and anxiety‐like behaviours and whole body cortisol levels (Kyzar and Kalueff, ). Ketamine, a dissociative psychedelic, produces a dose‐dependent anxiolytic effect in the zebrafish and decreases whole body cortisol levels (De Campos et al, ). The deliriant psychedelic atropine affects cholinergic neural activity in the zebrafish (Park et al, ).…”

Section: Zebrafish Sensitivity To Cns Drug Classesmentioning

confidence: 99%

Zebrafish models in neuropsychopharmacology and CNS drug discovery

Khan

Collier

Meshalkina

et al. 2017

British J Pharmacology

140

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Despite the high prevalence of neuropsychiatric disorders, their aetiology and molecular mechanisms remain poorly understood. The zebrafish (Danio rerio) is increasingly utilized as a powerful animal model in neuropharmacology research and in vivo drug screening. Collectively, this makes zebrafish a useful tool for drug discovery and the identification of disordered molecular pathways. Here, we discuss zebrafish models of selected human neuropsychiatric disorders and drug-induced phenotypes. As well as covering a broad range of brain disorders (from anxiety and psychoses to neurodegeneration), we also summarize recent developments in zebrafish genetics and small molecule screening, which markedly enhance the disease modelling and the discovery of novel drug targets.

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“…In addition, Newman et al (2012) observed that acute exposure to ketamine followed water self-administration in mice reduced the number of attack bites frequency and ketamine did not interact with ethanol on enhancing aggressive behavior. In another study, we observed that ketamine also increased hyperactivity in adult zebrafish at the doses of 40 and 60 mg L -1 , which can explain the higher values for mirror biting duration as a hyperactivity consequence [13] . Dopamine and serotonin are involved in the modulation of aggressive behavior [19] .…”

Section: Resultsmentioning

confidence: 82%

“…Zebrafish were exposed to ketamine or drug-free water for 20 minutes in a 1000 mL tank and then subjected to behavioral assays. The experimental groups were exposed to concentrations of 5, 20, 40 or 60 mg L -1 of ketamine, selected according to other published studies [11][12][13] . The ketamine used in this study was the injectable medication containing ketamine hydrochloride (Dopalen®, Ceva).…”

Section: Pharmacological Manipulationsmentioning

confidence: 99%

Investigation of ketamine pharmacological modulation of aggressive behavior in adult zebrafish

Campos

Martinis

2016

Neurosci Commun

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Ketamine is an anesthetic agent which in recent years has gained prominence due to its antidepressant properties. However, the adverse effects resulting from the acute administration of this drug have been reported and are a challenge for use of ketamine as an antidepressant. The aim of this study was the characterization of the acute effects of ketamine in states of aggressiveness in adult zebrafish (Danio rerio). Our results showed that ketamine didn't induce aggressive-like behaviors, at sub-anesthetic doses. However, these findings suggest that biochemical and neurochemical studies must be conducted to investigate the effects of ketamine on aggressiveness at molecular level in adult zebrafish.

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Ketamine induces anxiolytic effects in adult zebrafish: A multivariate statistics approach

Cited by 21 publications

References 45 publications

Zebrafish Larvae Carrying a Splice Variant Mutation in cacna1d: A New Model for Schizophrenia-Like Behaviours?

Zebrafish Larvae Carrying a Splice Variant Mutation in cacna1d: A New Model for Schizophrenia-Like Behaviours?

Zebrafish models in neuropsychopharmacology and CNS drug discovery

Investigation of ketamine pharmacological modulation of aggressive behavior in adult zebrafish

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