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Abstract Background The clinical utility of whole genome sequencing (WGS) in paediatric cancer has been demonstrated in recent years. WGS has been routinely available in the National Health Service (NHS) England for all children with cancer in England since 2021, but its uptake has been variable geographically. To explore the underlying barriers to routine use of WGS in this population across England and more widely in the United Kingdom (UK) and the Republic of Ireland (ROI), a one-day workshop was held in Cambridge, United Kingdom in October 2022. Methods Following a series of talks, delegates participated in open, round-table discussions to outline local and broader challenges limiting routine WGS for diagnostic work-up for children with cancer in their Principal Treatment Centres (PTCs) and Genomic Laboratory Hubs (GLHs). Within smaller groups, delegates answered structured questions regarding clinical capability, education and training needs, and workforce competence and requirements. Data was recorded, centrally collated, and analysed following the event using thematic analysis. Results Sixty participants attended the workshop with broad representation from the 20 PTCs across the UK and ROI and the seven GLHs in England. All healthcare professionals involved in the WGS pathway were represented, including paediatric oncologists, clinical geneticists, clinical scientists, and histopathologists. The main themes highlighted by the group in ensuring equitable access to WGS identified were: lack of knowledge equity between NHS trusts, with a perception of WGS being for research only; and perception of lack of financial support for the clinical process surrounding WGS, including lack of time to take informed consent from patients. The latter also included limited trained staff available for data interpretation, affecting the turnaround time for reporting. Finally, the need for an integrated digital pathway to order, track, and return data to clinicians was highlighted. Conclusion At the workshop, the general motivation for including WGS in the diagnostic work up for children with cancer was high throughout the UK, however a perceived lack of resources and education opportunities limit the widespread use of this commissioned assay. This workshop has led to some recommendations to increase access to WGS in this population in England and more widely in the devolved national of the UK and the ROI.

Abstract Coccidioides is the fungal causative agent of Valley fever, a primarily pulmonary disease caused by inhalation of fungal arthroconidia, or spores. Although Coccidioides has been an established pathogen for 120 years and is responsible for hundreds of thousands of infections per year, little is known about when and where infectious Coccidioides arthroconidia are present within the ambient air in endemic regions. Long-term air sampling programs provide a means to investigate these characteristics across space and time. Here we present data from > 18 months of collections from 11 air sampling sites across the Phoenix, Arizona, metropolitan area. Overall, prevalence was highly variable across space and time with no obvious spatial or temporal correlations. Several high prevalence periods were identified at select sites, with no obvious spatial or temporal associations. Comparing these data with weather and environmental factor data, wind gusts and temperature were positively associated with Coccidioides detection, while soil moisture was negatively associated with Coccidioides detection. These results provide critical insights into the frequency and distribution of airborne arthroconidia and the associated risk of inhalation and potential disease that is present across space and time in a highly endemic locale.

Whole-genome sequencing has advanced our understanding of the population structure of the pathogenic species complex Cryptococcus gattii, which has allowed for the phylogenomic specification of previously described major molecular type groupings and novel lineages. Recently, isolates collected in Mexico in the 1960s were determined to be genetically distant from other known molecular types and were classified as VGVI. We sequenced four clinical isolates and one veterinary isolate collected in the southwestern United States and Argentina from 2012 to 2021. Phylogenomic analysis groups these genomes with those of the Mexican VGVI isolates, expanding VGVI into a clade and establishing this molecular type as a clinically important population. These findings also potentially expand the known Cryptococcus ecological range with a previously unrecognized endemic area.

This paper presents flight and guidance control systems that can accurately land a fixed-wing unmanned aerial vehicle onto a small moving platform. The flight control system uses a hybrid architecture that combines classical control with model predictive control. The guidance control system uses a guidance algorithm, waypoint scheduler and state machine to allow the aircraft to complete circuits around the airfield. A prediction algorithm calculates the touchdown point between the aircraft and the moving platform. The state machine provides references to the flight control system to allow the aircraft to reach this touchdown point. The control system is implemented in PX4 autopilot software and verified using simulation. A fixed-wing aircraft is constructed using a model airframe with a Pixhawk 4 autopilot hardware and other additional hardware components. In simulation, the control system lands the aircraft on a moving platform with an accuracy of 22 cm, while for the practical moving platform landing, the control system lands the aircraft with an accuracy of 75 cm. Preparations are being done to perform the final practical moving platform landing tests.

ISSUES AND PURPOSE: The development of a multiunit-based certificate program to promote retention by increasing experienced pediatric nurses' knowledge, skills, and professional role development through a blend of didactic, clinical, and mentoring components. CONCLUSIONS: The certificate group demonstrated an increase in knowledge and skill, advanced leadership role acquisition, promotion, certification, and graduate school matriculation, and achieved a 95% retention rate within the organization. PRACTICE IMPLICATIONS: With support from management and multidisciplinary team members, a certificate program like this can be implemented in a variety of settings and specialties. [ABSTRACT FROM AUTHOR]

Environmental factors play a role in the development and severity of neuropsychiatric disorders. Externalizing disorders are characterized by disruptive, impulsive, and often aggressive behaviors, including difficulties with self-control, rule-breaking, and a tendency to act out in ways that may harm oneself or others. Externalizing disorders frequently co-occur with internalizing disorders, such as anxiety. Individuals experiencing both externalizing/internalizing disorders are often among the most likely to seek healthcare services, as this co-occurrence is associated with more severe symptomatology and greater functional impairment. Here, we investigated the impact of environmental enrichment (EE) on adgrl3.1, a gene associated with impulsivity and attention deficits in zebrafish (Danio rerio). This gene encodes a receptor involved in cell adhesion and signaling and has been linked to susceptibility to externalizing disorders. Zebrafish were reared in either standard or enriched environments (from 15 days-post fertilization), and attention, impulsivity, and anxiety-related phenotypes were assessed at adult stages (4 months-post fertilization) using the open field test and a 5-choice serial reaction time task. EE mitigated anxiety-related behaviors in adgrl3.1 knockouts, normalizing locomotor patterns and decreasing thigmotaxis. Although attention deficits were reduced in adgrl3.1 -/- fish reared in EE, impulsive behaviors were not. Together, these findings suggest that while environmental enrichment (EE) mitigates externalizing and internalizing symptoms in adgrl3.1 mutants, impulsivity remains less responsive to EE used in this study, indicating its distinct resistance to modulation., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Externalizing disorders (EDs) are characterized by outward-directed behaviors such as aggression and hyperactivity. They are influenced by gene-environment interactions, yet our understanding of the genetic predispositions and environmental contexts that give rise to them is incomplete. Additionally, people with EDs often exhibit comorbid internalizing symptoms, which can complicate the clinical presentation and treatment strategies. Following on from our previous studies, we examined genes x environment interaction as a risk factor for EDs by looking at internalizing and externalizing behaviors after social isolation. Specifically, we subjected adgrl3.1 knockout zebrafish - characterized by hyperactivity and impulsivity - to a 2-week social isolation protocol. We subsequently assessed the impact on anxiety-like behavior, abnormal repetitive behaviors, working memory, and social interactions. Genotype-specific additive effects emerged, with socially isolated adgrl3.1 knockout fish exhibiting intensified comorbid phenotypes, including increased anxiety, abnormal repetitive behaviors, reduced working memory, and altered shoaling, when compared to WT fish. The findings demonstrate that genetic predispositions interact with environmental stressors, such as social isolation, to exacerbate both externalizing and internalizing symptoms. This underlines the necessity for comprehensive diagnostic and intervention strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Despite being one of the most used laboratory species in biomedical, behavioral and physiological research, the nutritional requirements of zebrafish (Danio rerio) are poorly understood, and no standardized laboratory diet exists. Diet and feeding regimen can substantially impact the welfare of the fish and, in turn, experimental reproducibility. Consequently, the establishment of a standardized diet and feeding protocol for laboratory zebrafish is imperative to enhance animal welfare, guarantee research reproducibility and advance the economic and environmental sustainability of laboratory dietary practices. Here the aim of this systematic review is to provide an overview of the parameters that need to be standardized in future nutritional studies to facilitate future meta-analyses for confirmation of an optimal juvenile diet for growth. A comprehensive search was conducted in PubMed and Scopus to identify relevant studies published up to August 2023, and the studies were selected on the basis of the predefined inclusion/exclusion criteria. The databases yielded a total of 1,065 articles, of which 14 were included in this review. We conducted data extraction and risk-of-bias analysis in the included studies. Statistical comparisons for specific growth rate, weight gain (%) and length gain (%) parameters were performed to determine the optimal feed for enhanced juvenile growth. We identified significant heterogeneity and caveats to our findings owing to a lack of standardization of experimental conditions in nutritional studies. Our findings highlight an urgent need for research on zebrafish nutrition. Therefore, the standardized parameters we have reported here represent a critical starting point for studies., (© 2024. The Author(s).)

The reproducibility crisis in bioscience, characterized by inconsistent study results, impedes our understanding of biological processes and global collaborative studies offer a unique solution. This study is the first global collaboration using the zebrafish ( Danio rerio ) novel tank test, a behavioral assay for anxiety-like responses. We analyzed data from 20 laboratories worldwide, focusing on housing conditions and experimental setups. Our study included 488 adult zebrafish, tested for 5 min, focusing on a variety of variables. Key findings show females exhibit more anxiety-like behavior than males, underscoring sex as a critical variable. Housing conditions, including higher stocking densities and specific feed types, influenced anxiety levels. Optimal conditions (5 fish/L) and nutritionally rich feeds (e.g., rotifers), mitigated anxiety-like behaviors. Environmental stressors, like noise and transportation, significantly impacted behavior. We recommend standardizing protocols to account for sex differences, optimal stocking densities, nutritionally rich feeds, and minimizing stressors to improve zebrafish behavioral study reliability., Competing Interests: Competing Interest Statement: The authors declare no competing interests.

Zebrafish (Danio rerio) larvae offer a unique avenue for high-throughput in vivo investigation. The light/dark locomotor assay is widely used but lacks experimental consistency. Here, we present a protocol for a standardized light/dark assay by describing the steps for plating, acclimatizing larvae, performing the assay, and preparing drug exposure solutions. We also detail procedures for substance exposure and data analysis. For complete details on the use and execution of this protocol, please refer to Hillman et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Boredom, a complex emotional state with implications for mental health and well-being, has garnered attention across disciplines, yet remains relatively understudied in psychiatric research. Here, we explored the intricate relationship between trait-impulsivity, stress, and boredom across two studies. Participants completed self-report measures of trait-impulsivity and boredom and boredom-inducing tasks. Study 1, involving 80 participants (42 women and 38 men, aged 20-63), replicates previous findings, by demonstrating that impulsive individuals report greater boredom following a boring task. Study 2 then extends this, using 20 participants (9 women and 12 men, aged 18-24), to show that hypothalamic-pituitary-adrenal (HPA) axis activity, specifically heightened salivary cortisol responses, mediate the link between impulsivity and boredom following a boring task. Collectively, these results demonstrate that HPA axis activity may underline the relationship between trait-impulsivity and boredom by extending previous work and offering a novel insight into potential mechanisms. These findings offer promise for personalised interventions, designed for high impulsivity individuals, to alleviate the negative impacts of boredom and potentially break the identified feedback loop., Competing Interests: Declaration of competing interest We have no known conflict of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Decision-making in animals often involves choosing actions while navigating the environment, a process markedly different from static decision paradigms commonly studied in laboratory settings. Even in decision-making assays in which animals can freely locomote, decision outcomes are often interpreted as happening at single points in space and single moments in time, a simplification that potentially glosses over important spatiotemporal dynamics. We investigated locomotor decision-making in Drosophila melanogaster in Y-shaped mazes, measuring the extent to which their future choices could be predicted through space and time. We demonstrate that turn-decisions can be reliably predicted from flies' locomotor dynamics, with distinct predictability phases emerging as flies progress through maze regions. We show that these predictability dynamics are not merely the result of maze geometry or wall-following tendencies, but instead reflect the capacity of flies to move in ways that depend on sustained locomotor signatures, suggesting an active, working memory-like process. Additionally, we demonstrate that fly mutants known to have sensory and information-processing deficits exhibit altered spatial predictability patterns, highlighting the role of visual, mechanosensory, and dopaminergic signaling in locomotor decision-making. Finally, highlighting the broad applicability of our analyses, we generalize our findings to other species and tasks. We show that human participants in a virtual Y-maze exhibited similar decision predictability dynamics as flies. This study advances our understanding of decision-making processes, emphasizing the importance of spatial and temporal dynamics of locomotor behavior in the lead-up to discrete choice outcomes., Competing Interests: Competing Interest Statement: The authors declare no competing interests.

Zebrafish are a dynamic research model in the domains of neuropsychopharmacology, biological psychiatry and behaviour. Working with larvae ≤4 days post-fertilisation (dpf) offers an avenue for high-throughput investigation whilst aligning with the 3Rs principles of animal research. The light/dark assay, which is the most widely used behavioural assay for larval neuropharmacology research, lacks experimental reliability and standardisation. This study aimed to formulate a robust, reproducible and standardised light/dark behavioural assay using 4 dpf zebrafish larvae. Considerable between-batch and inter-individual variability was found, which we rectified with a normalisation approach to ensure a reliable foundation for analysis. We then identified that 5-min light/dark transition periods are optimal for locomotor activity. We also found that a 30-min acclimation in the light was found to produce significantly increased dark phase larval locomotion. Next, we confirmed the pharmacological predictivity of the standardised assay using ethanol which, as predicted, caused hyperlocomotion at low concentrations and hypolocomotion at high concentrations. Finally, the assay was validated by assessing the behavioural phenotype of hyperactive transgenic (adgrl3.1 -/- ) larvae, which was rescued with psychostimulant medications. Our standardised assay not only provides a clear experimental and analytical framework to work with 4 dpf larvae, but also facilitates between-laboratory collaboration using our normalisation approach., Competing Interests: Declaration of competing interest There is no conflict of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

Plastic additives are widely used in plastic production and are found in the environment owing to their widespread applications. Among these additives, N-butyl benzenesulfonamide (NBBS) and triphenyl phosphate (TPHP) are under international watchlist for evaluation, with limited studies on amphipods. Di-ethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP) are banned in some countries and categorised as substances of very high concern. This study aimed to investigate the effects of NBBS, TPHP, DEHP and DBP on the swimming activity of a coastal intertidal marine amphipod, Echinogammarus marinus. Furthermore, this study is the first to quantify startle response in E. marinus in response to light stimuli. Amphipods were exposed to 0, 0.5, 5, 50 and 500 μg/l concentrations of all test compounds. Swimming activity and startle responses were assessed by video tracking and analysis using an 8-min alternating dark and light protocol after exposure on days 7 and 14. We observed an overall compound and light effect on the swimming activity of E. marinus. A significant decrease in swimming distance was found in 500 μg/l NBBS and TPHP. We observed that the startle response in E. marinus had a latency period of >2 s and animals were assessed at 1 s and the sum of the first 5 s. There was a clear startle response in E. marinus during dark to light transition, evident with increased swimming distance. NBBS exposure significantly increased startle response at environmental concentrations, while significant effects were only seen in 500 μg/l TPHP at 5 s. We found no significant effects of DEHP and DBP on swimming behaviour at the concentrations assessed. The findings of this study affirm the necessity for a continuous review of plastic additives to combat adverse behavioural effects that may be transferable to the population levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Both sleep deprivation and hypoxia have been shown to impair executive function. Conversely, moderate intensity exercise is known to improve executive function. In a multi-experiment study, we tested the hypotheses that moderate intensity exercise would ameliorate any decline in executive function after i) three consecutive nights of partial sleep deprivation (PSD) (Experiment 1) and ii) the isolated and combined effects of a single night of total sleep deprivation (TSD) and acute hypoxia (Experiment 2)., Methods: Using a rigorous randomised controlled crossover design, 12 healthy participants volunteered in each experiment (24 total, 5 females). In both experiments seven executive function tasks (2-choice reaction time, logical relations, manikin, mathematical processing, 1-back, 2-back, 3-back) were completed at rest and during 20 min semi-recumbent, moderate intensity cycling. Tasks were completed in the following conditions: before and after three consecutive nights of PSD and habitual sleep (Experiment 1) and in normoxia and acute hypoxia (F I O 2  = 0.12) following one night of habitual sleep and one night of TSD (Experiment 2)., Results: Although the effects of three nights of PSD on executive functions were inconsistent, one night of TSD (regardless of hypoxic status) reduced executive functions. Significantly, regardless of sleep or hypoxic status, executive functions are improved during an acute bout of moderate intensity exercise., Conclusion: These novel data indicate that moderate intensity exercise improves executive function performance after both PSD and TSD, regardless of hypoxic status. The key determinants and/or mechanism(s) responsible for this improvement still need to be elucidated. Future work should seek to identify these mechanisms and translate these significant findings into occupational and skilled performance settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Plastics contain a mixture of chemical additives that can leach into the environment and potentially cause harmful effects on reproduction and the endocrine system. Two of these chemicals, N-butyl benzenesulfonamide (NBBS) and triphenyl phosphate (TPHP), are among the top 30 organic chemicals detected in surface and groundwater and are currently placed on international watchlist for evaluation. Although bans have been placed on legacy pollutants such as diethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP), their persistence remains a concern. This study aimed to examine the impact of plastic additives, including NBBS, TPHP, DBP, and DEHP, on the reproductive behaviour and male fertility of the marine amphipod Echinogammarus marinus. Twenty precopulatory pairs of E. marinus were exposed to varying concentrations of the four test chemicals to assess their pairing behaviour. A high-throughput methodology was developed and optimised to record the contact time and re-pair time within 15 min and additional point observations for 96 h. The study found that low levels of NBBS, TPHP, and DEHP prolonged the contact and re-pairing time of amphipods and the proportion of pairs reduced drastically with re-pairing success ranging from 75% to 100% in the control group and 0%-85% in the exposed groups at 96 h. Sperm count declined by 40% and 60% in the 50 μg/l and 500 μg/l DBP groups, respectively, whereas TPHP resulted in significantly lower sperms in 50 μg/l exposed group. Animals exposed to NBBS and DEHP showed high interindividual variability in all exposed groups. Overall, this study provides evidence that plastic additives can disrupt the reproductive mechanisms and sperm counts of amphipods at environmentally relevant concentrations. Our research also demonstrated the usefulness of the precopulatory pairing mechanism as a sensitive endpoint in ecotoxicity assessments to proactively mitigate population-level effects in the aquatic environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Social isolation has detrimental health effects, but the underlying mechanisms are unclear. Here, we investigated the impact of 2 weeks of isolation on behavior and gene expression in the central nervous system at different life stages of zebrafish. Results showed that socially deprived young adult zebrafish experienced increased anxiety, accompanied by changes in gene expression. Most gene expression patterns returned to normal within 24 hours of reintroduction to a social environment, except angptl4, which was upregulated after reintroduction, suggesting an adaptive mechanism. Similarly, aging zebrafish displayed heightened anxiety and increased central nervous system expression of angptl4 during isolation, but effects were reversed upon reintroduction to a social group. The findings imply that angptl4 plays a homeostatic role in response to social isolation, which varies across the lifespan. The study emphasizes the importance of social interactions for psychological well-being and highlights the negative consequences of isolation, especially in older individuals. Further research may unravel how social isolation affects angptl4 expression and its developmental and aging effects., Competing Interests: Disclosure statement There is no conflict of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Externalizing disorders (ED) are a cause of concern for public health, and their high heritability makes genetic risk factors a priority for research. Adhesion G-Protein-Coupled Receptor L3 (ADGRL3) is strongly linked to several EDs, and loss-of-function models have shown the impacts of this gene on several core ED-related behaviors. For example, adgrl3.1 -/- zebrafish show high levels of hyperactivity. However, our understanding of the mechanisms by which this gene influences behavior is incomplete. Here we characterized, for the first time, externalizing behavioral phenotypes of adgrl3.1 -/- zebrafish and found them to be highly impulsive, show risk-taking in a novel environment, have attentional deficits, and show high levels of hyperactivity. All of these phenotypes were rescued by atomoxetine, demonstrating noradrenergic mediation of the externalizing effects of adgrl3.1. Transcriptomic analyses of the brains of adgrl3.1 -/- vs. wild-type fish revealed several differentially expressed genes and enriched gene clusters that were independent of noradrenergic manipulation. This suggests new putative functional pathways underlying ED-related behaviors, and potential targets for the treatment of ED., (© 2023. Springer Nature Limited.)

The acquisition of executive skills such as working memory, decision-making and adaptive responding occur at different stages of central nervous system development. Zebrafish (Danio rerio) are increasingly used in behavioural neuroscience for complex behavioural tasks, and there is a critical need to understand the ontogeny of their executive functions. Zebrafish across developmental stages (4, 7, 14, 30 and 90 days post fertilisation (dpf)), were assessed to track development of working memory (WM) and behavioural flexibility (BF) using the free movement pattern Y-maze (FMP Y-maze). Several differences in both WM and BF were identified during the transition from yolk-dependent to independent feeding. Specifically, WM is evident in all age groups, even from 4 dpf. However, BF is not developed until larvae start free feeding, and show significant improvement thereafter, with young adults (90 dpf) demonstrating the most well-defined BF. We demonstrate, for the first time, objective WM processes in 4 dpf zebrafish larvae. This suggests that those wishing to study WM in zebrafish may be able to do so from 4 dpf, thus drastically increasing throughput. In addition, we show that zebrafish follow distinct stages of cognitive development and age-related changes during the early developmental period. Finally, our findings indicate distinct WM and BF mechanisms, which may be useful to study for translational purposes., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Spatial anxiety (i.e., feelings of apprehension and fear about navigating everyday environments) can adversely impact people's ability to reach desired locations and explore unfamiliar places. Prior research has either assessed spatial anxiety as an individual-difference variable or measured it as an outcome, but there are currently no experimental inductions to investigate its causal effects. To address this lacuna, we developed a novel protocol for inducing spatial anxiety within a virtual environment. Participants first learnt a route using directional arrows. Next, we removed the directional arrows and randomly assigned participants to navigate either the same route (n = 22; control condition) or a variation of this route in which we surreptitiously introduced unfamiliar paths and landmarks (n = 22; spatial-anxiety condition). The manipulation successfully induced transient (i.e., state-level) spatial anxiety and task stress but did not significantly reduce task enjoyment. Our findings lay the foundation for an experimental paradigm that will facilitate future work on the causal effects of spatial anxiety in navigational contexts. The experimental task is freely available via the Open Science Framework ( https://osf.io/uq4v7/ )., (© 2022. The Author(s).)

Stress, trait impulsivity, and emotional dysregulation are independent predictors of alcohol use and misuse, but little is known about the potential mechanisms that link these risk factors together. To address this issue, we carried out an exploratory cross-sectional study, on UK-based participants. Our preregistered, hypothesised theoretical framework was that emotional dysregulation mediates the association between cumulative lifetime stressor exposure and lifetime alcohol use. We also hypothesised that heightened impulsivity would strengthen these relations. As hypothesised, emotional dysregulation fully mediated the relation between cumulative lifetime stressor exposure and lifetime alcohol use. Several facets of impulsivity moderated these associations. For example, as levels of negative urgency increased, the associations between cumulative lifetime stressor exposure and emotional dysregulation, emotional dysregulation and lifetime alcohol use, and lifetime stress exposure and lifetime alcohol use, via emotional dysregulation, strengthened. These preliminary findings propose a theoretically framed model which integrates several prominent risk-factors for alcohol misuse, extending prior research and generating interesting and novel lines of enquiry for longitudinal and cross-cultural analyses. The findings also highlight the potential clinical utility of screening for lifetime stress exposure while tailoring personalised treatment interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

ADHD is a highly prevalent neurodevelopmental disorder. The first-line therapeutic for ADHD, methylphenidate, can cause serious side effects including weight loss, insomnia, and hypertension. Therefore, the development of non-stimulant-based therapeutics has been prioritized. However, many of these also cause other effects, most notably somnolence. Here, we have used a uniquely powerful genetic model and unbiased drug screen to identify novel ADHD non-stimulant therapeutics. We first found that adgrl3.1 null (adgrl3.1 -/- ) zebrafish larvae showed a robust hyperactive phenotype. Although the hyperactivity was rescued by three ADHD non-stimulant therapeutics, all interfered significantly with sleep. Second, we used wild-type zebrafish larvae to characterize a simple behavioral phenotype generated by atomoxetine and screened the 1200 compound Prestwick Chemical Library® for a matching behavioral profile resulting in 67 hits. These hits were re-assayed in the adgrl3.1 -/- . Using the previously identified non-stimulants as a positive control, we identified four compounds that matched the effect of atomoxetine: aceclofenac, amlodipine, doxazosin, and moxonidine. We additionally demonstrated cognitive effects of moxonidine in mice using a T-maze spontaneous alternation task. Moxonidine, has high affinity for imidazoline 1 receptors. We, therefore, assayed a pure imidazoline 1 agonist, LNP599, which generated an effect closely matching other non-stimulant ADHD therapeutics suggesting a role for this receptor system in ADHD. In summary, we introduce a genetic model of ADHD in zebrafish and identify five putative therapeutics. The findings offer a novel tool for understanding the neural circuits of ADHD, suggest a novel mechanism for its etiology, and identify novel therapeutics., (© 2022. The Author(s).)

Early-life adversity impacts on anxiety-related behaviors in adulthood. The effects of such adversity not only affect the animal itself, but can be passed on transgenerationally. Pervasive effects of experimentally-induced early-life stress (ELS) have been documented in adult zebrafish but it is not clear if this can be passed on via the germline. Here, we investigated the effects of ELS across three generations, by analyzing the responses of adult animals exposed to ELS in two different anxiety-related tasks, as well as in social behavior, memory, and cognition. Animals exposed to ELS (at 7 days-post-fertilization) showed a marked attenuation of specific anxiety-related behaviors (F 0 ) as adults, and these alterations were maintained across two subsequent generations (F 1 and F 2 ). This suggest zebrafish may be a useful model organism to study the transgenerational effects of ELS, and how this pertains to (for example) neuropsychiatric disorders. In addition, our data may naturally provoke questions regarding consideration of the environment of laboratory-housed zebrafish at early developmental stages. In particular, more work may be necessary to determine how different environmental stressors could affect data variability across laboratories., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Salient landmarks enhance route learning. We hypothesised that semantically salient nostalgic landmarks would improve route learning compared to non-nostalgic landmarks. In two experiments, participants learned a route through a computer-generated maze using directional arrows and wall-mounted pictures. On the test trial, the arrows were removed, and participants completed the maze using only the pictures. In the nostalgia condition, pictures were of popular music artists and TV characters from 5 to 10 years ago. In the control condition, they were recent pictures of these same artists and characters. In Experiment 1, in the test trial, participants in the nostalgia condition completed the maze faster than controls. Experiment 2 conceptually replicated these findings and extended them by exploring boundary conditions. Participants had to learn two mazes sequentially. In Maze 1, we placed nostalgic/control landmarks only at non-decision points (whereas we placed them at decision points in Experiment 1). In Maze 2, we placed nostalgic/control landmarks at decision points during acquisition but removed them in the test trial (whereas they were present in the test trial in Experiment 1). In both mazes, participants in the nostalgia (compared to control) condition completed the test trial faster.

We explored (1) self-reported changes in alcohol use during the pandemic in the UK and (2) the extent to which self-reported inhibitory control and/or stress were associated with any change in drinking behaviour. We used a UK-based cross-sectional online survey administered to four nationally representative birth cohorts ( N  = 13,453). A significant minority of 30- (29.08%) and 50-year-olds (26.67%) reported drinking more, and between 32.23 and 45.02% of respondents reported feeling more stressed depending on the cohort. Stress was associated with hazardous drinking among 30-year-olds (OR = 3.77, 95% CI 1.15 to 12.28). Impatience was associated with both increased alcohol use (1.14, 95% CI 1.06, 1.24) and hazardous drinking (1.20, 95% CI 1.05, 1.38) among 19-year-olds. Risk-taking was associated with hazardous drinking for 30-year-olds (OR = 1.18, 95% CI 1.05, 1.32). These data highlight concerns for those at risk of alcohol misuse and alcohol-related harm during COVID-19 lockdowns., Supplementary Information: The online version contains supplementary material available at 10.1007/s11469-021-00599-8., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2021.)

Background: Zebrafish are used in anxiety research as the species' naturalistic diving response to a new environment is a reliable and validated marker for anxiety-like behavior. One of the benefits of using zebrafish is the potential for high throughput drug screens in fish at the larval stage. However, at present, tests of anxiety in larvae and adults often measure different endpoints., New Method: Here, for the first time, we have adapted the novel tank diving response test for examining diving behavior in zebrafish larvae to assess anxiety-like behaviors at very early-stages (7 days-post-fertilization [dpf])., Comparison With Existing Methods: Current methods to examine anxiety in larvae can show low reliability, and measure different endpoints as in adults, thus calling into question their translational relevance., Results: We found that 7dpf zebrafish spent more time at the bottom of a small novel tank. We validated this as anxiety-like behaviors with diazepam reducing, and caffeine increasing the time spent in the bottom of the novel environment., Conclusions: This new automated and high-throughput screening tool has the potential use for screening of anxiogenic and anxiolytic compounds, and for studies aiming to better understand anxiety-like behaviors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of Interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Stress and genotype elicit changes in impulse control in a range of species that are attributable to adaptations in both the central and peripheral nervous system. We examined aspects of this mechanism in the horse by assessing the effect of a dopamine receptor genotype (DRD4) and central dopaminergic tone (measured via spontaneous blink rate [SBR] and behavioral initiation rate [BIR]), on measures of impulsivity, compulsivity (3-choice serial reaction time task) and sympathetic/ parasympathetic system balance (heart rate variability [HRV]). Genotype did not have a significant effect on any of the parameters measured. SBR but not BIR correlated significantly with levels of impulsivity. There was no clear association of HRV parameters with either measures of central dopaminergic activity or impulsivity/compulsivity. Overall, some elements of the data suggest that the horse may be a useful animal model for assessing the genetic and environmental factors that lead to the physiological and behavioral phenotype of human addiction, particularly when considering the relationship between central dopaminergic tone and impulsivity., (Copyright © 2022. Published by Elsevier Inc.)

Sex is an important biological variable that is widely recognized in studies of alcohol-related effects. Complementing clinical and preclinical rodent research, the zebrafish (Danio rerio) is the second most used laboratory species, and a powerful model organism in biomedicine. Like clinical and rodent models, zebrafish demonstrate overt sex differences in alcohol-related responses. Collectively, this evidence shows that the zebrafish becomes a sensitive model species to further probe in-depth sex differences commonly reported in alcohol research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Behavioural needs are highly motivated actions critical to a species survival and reproduction. Prolonged restriction of these behaviours can lead to stereotypic behaviours (SB) in captive animals, and this is particularly common in ungulate species. While risk factors for SB have been suggested for some ungulates, no study has integrated these findings to identify which aspects of ungulates' wild behavioural biology and captive husbandry are potential drivers for SB across this clade. We collated SB data from 15 236 individuals across 38 ungulate species from 95 sources, and determined species wild/free-ranging behaviour from 559 additional studies. Bayesian-phylogenetic statistical methods showed that ungulate behavioural needs relating to foraging and mating are particularly affected by captive environments, with promiscuous and browsing species showing the greatest prevalence of SB. Concentrate-only diets and lack of ad libitum feed substrates were also associated with high SB prevalence. This study identifies which ungulates are better suited to captive environments and which species require targeted husbandry, enrichment and breeding protocols in order to meet their behavioural needs. Our approach of applying Bayesian-phylogenetic inference to factors influencing SB within a clade can be used to identify other intrinsic and extrinsic risk factors of reduced animal health and welfare.

GRIA1 encodes the GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors, which are ligand-gated ion channels that act as excitatory receptors for the neurotransmitter L-glutamate (Glu). AMPA receptors (AMPARs) are homo- or heteromeric protein complexes with four subunits, each encoded by different genes, GRIA1 to GRIA4. Although GluA1-containing AMPARs have a crucial role in brain function, the human phenotype associated with deleterious GRIA1 sequence variants has not been established. Subjects with de novo missense and nonsense GRIA1 variants were identified through international collaboration. Detailed phenotypic and genetic assessments of the subjects were carried out and the pathogenicity of the variants was evaluated in vitro to characterize changes in AMPAR function and expression. In addition, two Xenopus gria1 CRISPR-Cas9 F 0 models were established to characterize the in vivo consequences. Seven unrelated individuals with rare GRIA1 variants were identified. One individual carried a homozygous nonsense variant (p.Arg377Ter), and six had heterozygous missense variations (p.Arg345Gln, p.Ala636Thr, p.Ile627Thr, and p.Gly745Asp), of which the p.Ala636Thr variant was recurrent in three individuals. The cohort revealed subjects to have a recurrent neurodevelopmental disorder mostly affecting cognition and speech. Functional evaluation of major GluA1-containing AMPAR subtypes carrying the GRIA1 variant mutations showed that three of the four missense variants profoundly perturb receptor function. The homozygous stop-gain variant completely destroys the expression of GluA1-containing AMPARs. The Xenopus gria1 models show transient motor deficits, an intermittent seizure phenotype, and a significant impairment to working memory in mutants. These data support a developmental disorder caused by both heterozygous and homozygous variants in GRIA1 affecting AMPAR function., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The use of multiple species to model complex human psychiatric disorders, such as ADHD, can give important insights into conserved evolutionary patterns underlying multidomain behaviors (e.g., locomotion, attention, and impulsivity). Here we discuss the advantages and challenges in modelling ADHD-like phenotypes in zebrafish (Danio rerio), a vertebrate species that has been widely used in neuroscience and behavior research. Moreover, multiple behavioral tasks can be used to model the core symptoms of ADHD and its comorbidities. We present a critical review of current ADHD studies in zebrafish, and how this species might be used to accelerate the discovery of new drug treatments for this disorder., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Rationale: Triangulation of approaches (i.e., using several tests of the same construct) can be extremely useful for increasing the robustness of the findings being widely used when working with behavioral testing, especially when using rodents as a translational model. Although zebrafish are widely used in neuropharmacology research due to their high-throughput screening potential for new therapeutic drugs, behavioral test battery effects following pharmacological manipulations are still unknown., Methods: Here, we tested the effects of an anxiety test battery and test time following pharmacological manipulations in zebrafish by using two behavioral tasks: the novel tank diving task (NTT) and the light-dark test (LDT). Fluoxetine and conspecific alarm substance (CAS) were chosen to induce anxiolytic and anxiogenic-like behavior, respectively., Results: For non-drug-treated animals, no differences were observed for testing order (NTT → LDT or LDT → NTT) and there was a strong correlation between performances on the two behavioral tasks. However, we found that during drug treatment, NTT/LDT responses are affected by the tested order depending on the test time being fluoxetine effects higher at the second behavioral task (6 min later) and CAS effects lower across time., Conclusions: Overall, our data supports the use of baseline behavior assessment using this anxiety test battery. However, when working with drug exposure, data analysis must carefully consider time-drug-response and data variability across behavioral tasks., (© 2021. The Author(s).)

Social behavior represents a beneficial interaction between conspecifics that is critical for maintaining health and wellbeing. Dysfunctional or poor social interaction are associated with increased risk of physical (e.g., vascular) and psychiatric disorders (e.g., anxiety, depression, and substance abuse). Although the impact of negative and positive social interactions is well-studied, their underlying mechanisms remain poorly understood. Zebrafish have well-characterized social behavior phenotypes, high genetic homology with humans, relative experimental simplicity and the potential for high-throughput screens. Here, we discuss the use of zebrafish as a candidate model organism for studying the fundamental mechanisms underlying social interactions, as well as potential impacts of social isolation on human health and wellbeing. Overall, the growing utility of zebrafish models may improve our understanding of how the presence and absence of social interactions can differentially modulate various molecular and physiological biomarkers, as well as a wide range of other behaviors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Zebrafish have been widely used to study anxiety-related phenotypes using the novel tank test (NTT). Although the NTT is well-characterized and commonly used by researchers, there is still a lack of information regarding how different experimental variables such as water quality can influence NTT performance. Zebrafish use different chemical cues and olfactory stimuli to communicate in water, so we predicted that water change frequency would affect cortisol, locomotion and anxiety-related parameters in the NTT., New Methods: After extensive literature research, we found that only about 18% of papers using NTT report partial or complete water changes between subjects. Here, we tested multiple zebrafish in the NTT using the same water up to 9 consecutive times (with no water change) and analyzed cortisol levels, as a stressrelated marker., Results: We found that when using the same water for more than 4 trials, data variability is increased and a higher number of extreme values is observed for the time spent in the top zone and immobility. Moreover, after 4 trials with no water change, increased cortisol levels are observed, indicating that animals show increased stressrelated responses with the lack of water changes., Conclusions: This study shows that lack of water change can significantly influence zebrafish stress-responses in the NTT. Altogether, behavioral experiments should avoid using the same water when testing multiple fish in the task, especially when looking at anxiety in the NTT., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Early-life stress (ELS) has been shown to result in a diverse array of long-lasting impacts; for example, increasing vulnerability to disease or building 'resilience' in adulthood. Previously, zebrafish (Danio rerio) have been used to understand the mechanisms by which ELS induces different behavioral phenotypes in adults, with alterations in both learning and anxiety observed in exposed individuals. Here, we subjected zebrafish larvae to chronic unpredictable early-life stress (CUELS) for 7 or 14 days, to investigate the impact on boldness towards a new environment and novel object, and stress-reactivity. We observed that 7 days of CUELS resulted in increased time spent in the top of a novel tank (indicating boldness) but did not alter approach to a novel object. Although CUELS did not affect stress-reactivity in terms of cortisol levels, decreased anxiety-like response to conspecific alarm substance (CAS) was observed in both ELS groups (7 and 14 days of CUELS). Therefore, for the first time, we observe a potential negative effect of CUELS by dampening the behavioral stress response following exposure to CAS. Overall, these data support the use of zebrafish as a translational model to study the broad range of ELS-induced permanent changes in behavior. It could also be used to investigate the mechanisms underlying both the positive and the negative effects of early-life adversity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Acute stressors are recurrent in multiple species' lives and can facilitate or impair cognition. The use of zebrafish (Danio rerio) as a translational species to understand the mechanisms by which stress induces different behavioral phenotypes has been widely studied. Two acute stressors are recognized when using this species: (1) conspecific alarm substance (CAS); and (2) net chasing. Here, we tested if CAS or net chasing would affect working memory and cognitive flexibility by testing performance in the FMP Y-maze after exposure to stress. We observed that CAS altered zebrafish behavioral phenotypes by increasing repetitive behavior; meanwhile, animals showed different patterns of repetitive behavior when exposed to net chasing, depending on the chasing direction. Because D1 receptors were previously studied as a potential mechanism underlying stress responses in different species, here, we pretreated fish with a D1/D5 agonist (SKF-38393) to assess whether this system plays a role in repetitive behavior in the FMP Y-maze. The pretreatment with D1/D5 agonist significantly decreased repetitive behavior in CAS exposed animals, and cortisol levels for both stressed groups, suggesting that the dopaminergic system plays an important role in zebrafish stress-related responses., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Exposure to anesthetic drugs is common in biomedical sciences being part of routine procedures in different translational species, however its impacts on memory and cognition are still debated, having different impacts depending on drug and age. The zebrafish ( Danio rerio ) is a translational species widely used in behavioral neuroscience, where tricaine methanesulfonate (MS222) is the most acceptable and used drug when conducting routine procedures. Based on this, we investigated the effects of MS222 (100 mg/l) in young adults and aging zebrafish 1, 2, 3, and 7 days after exposure. Animals' were submitted to the anesthetic procedure until loss of body posture, slowing of opercular movements and lack of response to tail touch with a plastic pipette were achieved, then further left in the drug for 3 min. After that, animals (6 mpf vs. 24 mpf) were transferred to a recovery tank until fully recovered and transferred back to their housing system until further testing in the free movement pattern (FMP) Y -maze, which assesses zebrafish working memory and cognitive lexibility. Young animals had significant impairment in their working memory and cognitive flexibility 1 and 2 days after the exposure to MS222, being fully recovered by day 3 and with no effects 7 days post drug exposure. Increased repetitions were also observed for animals exposed to MS222 which could indicate increased stress-related response in animals up to 2 days after drug exposure. No drug effect was observed in aging animals besides their natural decreased alternations and working memory. Overall, behavioral experiments after routine procedures using MS222 should be performed with caution and need to be delayed, at least 3 days after exposure where working memory, cognitive flexibility, and repetitive behavior are back to normal., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fontana, Alnassar and Parker.)

Background: Zebrafish are growing in use as a model for understanding drug dependence and addiction. Sensitization paradigms have been a useful tool in identifying mechanisms involved in drug-induced behavioral and neurological changes, but in zebrafish have tended to focus on locomotor, rather than cognitive, endpoints., Methods: Here, we used a novel method, the FMP Y-maze, which measures continuous performance through a series of repeated binary choices (L vs R), to establish a model for assessing parameters associated with psychostimulant-induced behavioral and cognitive sensitization in adult zebrafish., Results: Repeat, intermittent exposure to d-amphetamine (AMPH) for 14 days increased alternations (LRLR) in the maze, suggesting improved working memory, which was enhanced further following drug challenge after a short withdrawal period, suggesting behavioral sensitization. However, this cognitive enhancement coincided with a reduction in the use of other exploration strategies, hypolocomotion, and inhibition of cognitive flexibility. Like AMPH, exposure to nicotine (NIC) increased alternations following drug challenge after chronic treatment. Repeat NIC exposure appeared to induce both cognitive and psychomotor sensitization, as evidenced by increased working memory performance (alternations) and locomotor activity, without negatively impacting other search strategies or cognitive flexibility., Conclusion: Chronic treatment with AMPH or NIC boosts cognitive performance in adult zebrafish. Cognitive sensitization occurred with both drugs, resulting in enhanced working memory; however, repeat AMPH exposure, following a withdrawal period, resulted in inhibited cognitive flexibility, an effect not evident with repeat NIC exposure. Cognitive and behavioral sensitization paradigms in zebrafish could serve as a useful tool for assessing cognitive states which result in cognitive enhancing or impairing effects of drugs., (© 2021. The Author(s).)

Early-life stress can lead to two different behavioral responses: (1) increased susceptibility to psychiatric disorders or (2) resilience. Here, we created a chronic unpredictable early-life stress (CUELS) protocol to assess the effects of early experiences in adult zebrafish. Animals were exposed to mild stressors twice a day and the duration was varied between groups (0, 1, 3, 7 and 14 days of stress). The stressor consisted of light/dark cycle changes; social isolation; overcrowding; water changes; water cooling; mechanical stirring; water heating; and immersion in shallow water. Behavior was assessed at young stages (21 days post-fertilization - open field analysis) and adulthood (4-months-old - novel tank diving test, light/dark task, shoaling, free movement pattern Y-maze and Pavlovian fear conditioning). Cortisol levels were assessed to evaluate the impact of CUELS in the HPI axis. Zebrafish exposed to 7 days of CUELS showed a decreased anxiety-like phenotype in two behavioral tasks, presenting increased time spent in top and decreased time spent in the dark area. Animals exposed to 14 days of CUELS showed an opposite anxious phenotype compared to 3 and 7 days of CUELS. No significant changes were observed in memory and cognition, social behavior and cortisol levels. In general, 7 days of CUELS protocol decreased anxiety in young and adult zebrafish, and could be used to understand the mechanisms underlying early-life experiences-derived alterations in neural circuits of anxiety., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Healthy aging is associated with a decline in memory and executive function, which have both been linked with aberrant dopaminergic signaling. We examined the relationship between cognitive performance and dopamine function of young and aging zebrafish (Danio rerio). We revealed age-related decreases in working memory and cognitive flexibility in the Free-Movement Pattern (FMP) Y-maze. An increase in drd5 gene expression in aging adults coincided with a decrease in cognitive performance. Treatment with a D1/D5 receptor agonist (SKF-38393, 35 µM) 30 minutes prior to behavioral assessment resulted in improved working memory in aging zebrafish, but no effect in younger adults. However, an "overdosing" effect caused by agonist treatment resulted in downregulation of dat expression in 6-month old, treated zebrafish. The translational relevance of these findings was tested in humans by analyzing exploratory behavior in young-adult, 18-35-year olds, and aged adults, 70+ year olds, in a virtual FMP Y-maze. Our findings revealed similar age-related decline in working memory. Thus, strongly supporting zebrafish as a translational model of aging and cognitive decline., Competing Interests: Conflicts of Interest All authors disclose no conflict of interests., (Copyright © 2021. Published by Elsevier Inc.)

Numerous neurodegenerative and psychiatric disorders are associated with deficits in executive functions such as working memory and cognitive flexibility. Progress in developing effective treatments for disorders may benefit from targeting these cognitive impairments, the success of which is predicated on the development of animal models with validated behavioural assays. Zebrafish offer a promising model for studying complex brain disorders, but tasks assessing executive function are lacking. The Free-movement pattern (FMP) Y-maze combines aspects of the common Y-maze assay, which exploits the inherent motivation of an organism to explore an unknown environment, with analysis based on a series of sequential two-choice discriminations. We validate the task as a measure of working memory and executive function by comparing task performance parameters in adult zebrafish treated with a range of glutamatergic, cholinergic and dopaminergic drugs known to impair working memory and cognitive flexibility. We demonstrate the cross-species validity of the task by assessing performance parameters in adapted versions of the task for mice and Drosophila, and finally a virtual version in humans, and identify remarkable commonalities between vertebrate species' navigation of the maze. Together, our results demonstrate that the FMP Y-maze is a sensitive assay for assessing working memory and cognitive flexibility across species from invertebrates to humans, providing a simple and widely applicable behavioural assay with exceptional translational relevance.

Animal behaviour is becoming increasingly popular as an endpoint in ecotoxicology due to its increased sensitivity and speed compared to traditional endpoints. However, the widespread use of animal behaviours in environmental risk assessment is currently hindered by a lack of optimisation and standardisation of behavioural assays for model species. In this study, assays to assess swimming speed were developed for a model crustacean species, the brine shrimp Artemia franciscana . Preliminary works were performed to determine optimal arena size for this species, and weather lux used in the experiments had an impact on the animals phototactic response. Swimming speed was significantly lower in the smallest arena, whilst no difference was observed between the two larger arenas, suggesting that the small arena was limiting swimming ability. No significant difference was observed in attraction to light between high and low light intensities. Arena size had a significant impact on phototaxis behaviours. Large arenas resulted in animals spending more time in the light side of the arena compared to medium and small, irrespective of light intensity. The swimming speed assay was then used to expose specimens to a range of psychotropic compounds with varying modes of action. Results indicate that swimming speed provides a valid measure of the impacts of behaviour modulating compounds on A. franciscana . The psychotropic compounds tested varied in their impacts on animal behaviour. Fluoxetine resulted in increased swimming speed as has been found in other crustacean species, whilst oxazepam, venlafaxine and amitriptyline had no significant impacts on the behaviours measured. The results from this study suggest a simple, fast, high throughput assay for A. franciscana and gains insight on the impacts of a range of psychotropic compounds on the swimming behaviours of a model crustacean species used in ecotoxicology studies.

Early life stress (ELS) is defined as a short or chronic period of trauma, environmental or social deprivation, which can affect different neurochemical and behavioral patterns during adulthood. Zebrafish (Danio rerio) have been widely used as a model system to understand human neurodevelopmental disorders and display translationally relevant behavioral and stress-regulating systems. In this study, we aimed to investigate the effects of moderate ELS by exposing young animals (6-weeks postfertilization), for 3 consecutive days, to three stressors, and analyzing the impact of this on adult zebrafish behavior (16-week postfertilization). The ELS impact in adults was assessed through analysis of performance on tests of unconditioned memory (free movement pattern Y-maze test), exploratory and anxiety-related task (novel tank diving test), and social cohesion (shoaling test). Here, we show for the first time that moderate ELS increases the number of alternations in turn-direction compared to repetitions in the unconditioned Y-maze task, suggesting increased working memory, but has no effect on shoal cohesion, locomotor profile, or anxiety-like behavior. Overall, our data suggest that moderate ELS may be linked to adaptive flexibility which contributes to build "resilience" in adult zebrafish by improving working memory performance., (© 2020 The Authors. Developmental Psychobiology published by Wiley Periodicals LLC.)

There has been rapid growth in the use of larval zebrafish as a complementary vertebrate model for drug discovery, abuse liability and pharmacological toxicology, resulting in a huge increase in zebrafish facilities worldwide. However, many research groups working with zebrafish do not typically report the pH of husbandry conditions in methodologies, nor are the pH of drug treatments reported in many research articles. This unknown factor can be a major contributor in the differential effects of drug treatments. Therefore, as a case study, we tested the impact of altering pH of several drugs of abuse and assessed locomotor changes associated with a single drug concentration delivered at different pHs. We found that a change of a single pH unit, within the pH ranges commonly used in zebrafish husbandry, was enough to alter locomotor activity at a fixed drug concentration. Many pharmacological agents are dependent on environmental factors, such as pH, to determine bioavailability. Efficaciousness for many classes of drug is dependent on their ionization state in which shifts towards uncharged species can influence the easy of a drug crossing biological membranes. Thus, we urge users to report pH in husbandry methods and drug treatments to improve replicability and inter-study comparisons., (Copyright © 2020 Elsevier Inc. All rights reserved.)