Contingent stimulus delivery assay for zebrafish reveals a role for CCSER1 in alcohol preference

Nathan, Fatima Megala; Kibat, Caroline; Goel, Tanisha; Stewart, James; Claridge‐Chang, Adam; Mathuru, Ajay S.

doi:10.1111/adb.13126

Cited by 8 publications

(6 citation statements)

References 73 publications

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“…2022 [44] at the ZebraFish Facility (ZFF, Institute of Molecular and Cell Biology, A*STAR) in groups of 20-25 in 3-L tanks under standard facility conditions. Experimental protocols approved by the IACUC committee, Biological Resource Center at A*STAR (IACUC #201571) were followed for experiments with zebrafish.…”

Section: Organism Generation and Culturementioning

confidence: 99%

Evaluating the transmission risk of amyloid beta peptide via ingestion

Raine

Tolwinski

Gruber

et al. 2023

Preprint

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Recent reports suggest that amyloid beta (Aβ) peptides can exhibit prion-like pathogenic properties. Transmission of Aβ peptide and the development of associated pathologies after surgeries with contaminated instruments and intravenous or intracerebral inoculations have now been reported across fish, rodents, primates, and humans. This raises a worrying prospect of Aβ peptides also having other characteristics typical of prions, such as evasion of the digestive process. We asked if such transmission of Aβ aggregates via ingestion was possible. We made use of a transgenic Drosophila melanogaster line expressing human Aβ peptide prone to aggregation. Fly larvae were fed to adult zebrafish under two feeding schemes. The first was a short-term, high-intensity scheme over 48 hours to determine transmission and retention in the gut. The second, long-term, lower-intensity scheme specifically examined accumulation in the brain. The gut and brain tissues were examined through histological, Western blotting, and mass spectrometric analyses. None of the analyses could detect Aβ aggregates in the guts of zebrafish following ingestion, despite it being easily detectable in the feed. Additionally, there was no detectable accumulation of Aβ in the brain tissue or development of associated pathologies after prolonged feeding. While Aβ aggregates do not appear to be readily transmissible by ingestion across species, two prospects remain open. First, this mode of transmission, if occurring, may stay below a detectable threshold and may take much longer to manifest. A second possibility is that the human Aβ peptide may not be able to trigger self-propagation or aggregation of non-mammalian amyloid. Either possibility requires further investigation but suggests that Alzheimer′s Disease (AD) preventive measures to account for such transmission in humans are at present unwarranted.

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Section: Organism Generation and Culturementioning

confidence: 99%

Evaluating the transmission risk of amyloid beta peptide via ingestion

Raine

Tolwinski

Gruber

et al. 2023

Preprint

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“…Over time, this develops into an addiction. Several assays have been developed for mainly late larval/juvenile (> 3-4 weeks) and adult zebrafish to study addiction behaviors, including conditioned place preference (CPP) assays where the animal associates the drug with a neutral environmental stimulus (Tzschentke, 2007;Webb et al, 2009;Mathur et al, 2011;Collier and Echevarria, 2013) and self-administration assays in which the zebrafish triggers the delivery of addictive substances by its own actions (Bossé and Peterson, 2017;Nathan et al, 2022). Müller et al (2020) reviews these and additional assays in more detail.…”

Section: Responses To Addictive Substancesmentioning

confidence: 99%

Larval Zebrafish as a Model for Mechanistic Discovery in Mental Health

Tan

Ang

Wee

2022

Front. Mol. Neurosci.

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Animal models are essential for the discovery of mechanisms and treatments for neuropsychiatric disorders. However, complex mental health disorders such as depression and anxiety are difficult to fully recapitulate in these models. Borrowing from the field of psychiatric genetics, we reiterate the framework of ‘endophenotypes’ – biological or behavioral markers with cellular, molecular or genetic underpinnings – to reduce complex disorders into measurable behaviors that can be compared across organisms. Zebrafish are popular disease models due to the conserved genetic, physiological and anatomical pathways between zebrafish and humans. Adult zebrafish, which display more sophisticated behaviors and cognition, have long been used to model psychiatric disorders. However, larvae (up to 1 month old) are more numerous and also optically transparent, and hence are particularly suited for high-throughput screening and brain-wide neural circuit imaging. A number of behavioral assays have been developed to quantify neuropsychiatric phenomena in larval zebrafish. Here, we will review these assays and the current knowledge regarding the underlying mechanisms of their behavioral readouts. We will also discuss the existing evidence linking larval zebrafish behavior to specific human behavioral traits and how the endophenotype framework can be applied. Importantly, many of the endophenotypes we review do not solely define a diseased state but could manifest as a spectrum across the general population. As such, we make the case for larval zebrafish as a promising model for extending our understanding of population mental health, and for identifying novel therapeutics and interventions with broad impact.

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“…While the behavioral response of larval zebrafish to acute exposures to nicotine (acute nicotine response, ANR) is routinely used in drug-development projects, they do not allow larval zebrafish to titrate their exposure to nicotine as in self-administration tests in rodents. Behavioral choice tests for drugs of dependence are less developed in larval zebrafish compared to adult zebrafish ( Schneider, 2017 ; Nathan et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…To better understand the underlying mechanisms of nicotine use, behavioral choice tests in which animals can self-administer drugs are more suitable ( Perkins, 1999 ). The self-administration experiments for drugs of abuse in rodents have been essential for the discovery of neuronal mechanisms regulating nicotine use but are more difficult to conduct in zebrafish and especially in larval zebrafish ( Krishnan et al, 2014 ; Bosse and Peterson, 2017 ; Bosse et al, 2021a , b ; Gallois et al, 2022 ; Nathan et al, 2022 ). Based on mazes that have been successfully used for rodents and single-chamber behavioral choice tests for larval zebrafish, we developed a three-compartment gradient-maze for measuring nicotine-seeking and avoidance behavior of individual larval zebrafish.…”

Section: Introductionmentioning

confidence: 99%

Identification of nicotine-seeking and avoiding larval zebrafish using a new three-choice behavioral assay

Schneider

Pearson

Harris

et al. 2023

Front. Mol. Neurosci.

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IntroductionNicotine dependence is one of the main causes of preventable diseases in the United States. Nicotine-seeking and avoidance behavioral assays in larval zebrafish could be used for identifying potential new pharmacotherapeutics in an early phase of drug discovery and could facilitate the identification of genes and genomic variations associated with nicotine-seeking and avoidance behavior.MethodsA new three-choice behavioral assay has been developed for the identification of nicotine-seeking and avoiding larval zebrafish. The three choices are represented by three compartments of a gradient maze. Video-recording and subsequent quantitative analysis of the swimming track was carried out using EthovisionXT (Noldus).ResultsThree behavioral phenotypes could be identified. Nicotine-seeking larval zebrafish occupied nicotine compartments for longer periods and entered the nicotine-containing compartments most frequently. Nicotine-avoiders spent most of the cumulative time in the water compartment or entered the water compartment most frequently. Non-seekers remained in the center compartment for most of the time. In the gradient maze, about 20–30% of larval zebrafish had a preference for low nicotine concentrations whereas nicotine avoidance was stronger at higher nicotine concentrations. Lower concentrations of nicotine (0.63 μM, 6.3 μM) resulted in higher percentages of nicotine seekers whereas high nicotine concentrations (63 μM, 630 µM) resulted in higher percentages of nicotine avoiders. Pre-treatment of larval zebrafish with nicotine slightly increased the percentage of nicotine avoiders at lower nicotine concentrations. Treatment with varenicline strongly increased the percentage of nicotine avoiders at lower nicotine concentrations.ConclusionThe results show that larval zebrafish have individual preferences for nicotine that could change with drug treatment. The three-choice gradient maze assay for larval zebrafish provides a new testing paradigm for studying the molecular and cellular mechanisms of nicotine action and the discovery of potential new pharmacotherapeutics for the treatment of smoking cessation.

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Contingent stimulus delivery assay for zebrafish reveals a role for CCSER1 in alcohol preference

Cited by 8 publications

References 73 publications

Evaluating the transmission risk of amyloid beta peptide via ingestion

Evaluating the transmission risk of amyloid beta peptide via ingestion

Larval Zebrafish as a Model for Mechanistic Discovery in Mental Health

Identification of nicotine-seeking and avoiding larval zebrafish using a new three-choice behavioral assay

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