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Music therapy has long been used as a non-pharmacological intervention to improve cognitive function and mood in humans. Mounting rodent evidence also supports beneficial impact of music exposure on animal cognitive performance. The zebrafish (Danio rerio) is an important emerging aquatic animal model in translational biomedical and neuroscience research. Here, we evaluate the effects of intermittent (2-h or 6-h twice daily) and continuous (24-h) solfeggio-frequency music exposure on behavioral, cognitive and endocrine parameters in adult zebrafish whose circadian rhythm was disturbed by a 24-h light exposure. Overall, a 24-h light exposure stress evokes overt cognitive deficits in the inhibitory avoidance test and elevates zebrafish whole-body cortisol levels. However, these effects were reversed by solfeggio-frequency music exposure for 2 or 6 h twice daily, and by continuous 24-h exposure. Collectively, these findings suggest a positive modulation of cognitive and endocrine responses in adult zebrafish by environmental enrichment via the long-term exposure to music, and reinforces zebrafish as a robust, sensitive model organism for neurocognitive and neuroendocrine research.

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Stress response is essential for the organism to quickly restore physiological homeostasis disturbed by various environmental insults. In addition to well-established physiological cascades, stress also evokes various brain and behavioral responses. Aquatic animal models, including the zebrafish (Danio rerio), have been extensively used to probe pathobiological mechanisms of stress and stress-related brain disorders. Here, we critically discuss the use of zebrafish models for studying mechanisms of stress and modeling its disorders experimentally, with a particular cross-taxon focus on the potential evolution of stress responses from zebrafish to rodents and humans, as well as its translational implications.

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Sex differences influence human and animal behavioral and pharmacological responses. The zebrafish (Danio rerio) is a powerful, popular model system in neuroscience and drug screening. However, the impact of zebrafish sex differences on their behavior and drug responses remains poorly understood. Here, we evaluate baseline anxiety-like behavior in adult male and female zebrafish, and its changes following an acute 30-min exposure to 800-µM scopolamine, a common psychoactive anticholinergic drug. Overall, we report high baseline anxiety-like behavior and more individual variability in locomotion in female zebrafish, as well as distinct, sex-specific (anxiolytic-like in females and anxiogenic-like in males) effects of scopolamine. Collectively, these findings reinforce the growing importance of zebrafish models for studying how both individual and sex differences shape behavioral and pharmacological responses.

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Typically triggered by stress, anxiety disorders are most common and widespread mental illnesses. The zebrafish (Danio rerio) is rapidly becoming an important aquatic model species in stress research and central nervous system (CNS) drug screening. Paracetamol is currently the most prescribed medication for pain and fever, and is among the most used drugs globally. However, its CNS effects, especially on anxiety, in both clinical and animal studies remain poorly understood. Capitalizing on zebrafish as a powerful model system, here we evaluate the effects of paracetamol on anxiety-like behavior in adult fish, and its changes following an acute stress exposure. Overall, we report an anxiolytic-like profile of acute paracetamol treatment, and its alleviation of stress-evoked anxiety, in adult short-fin wild type zebrafish. Collectively, these findings suggest complex neuroactive effects of paracetamol, and reinforce the growing importance of zebrafish models for drug screening, including the search for novel putative anti-stress therapies.

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Estradiol (17ß-estradiol, E2) is a crucial estrogen hormone that regulates sexual, cognitive, social and affective behaviors in various species. However, complex central nervous system (CNS) effects of E2, including its activity in males, remain poorly understood. The zebrafish (Danio rerio) is rapidly becoming a powerful novel model system in translational neuroscience research. Here, we evaluate the effects of a single 24-h exposure to 20 µg/L of E2 on behavioral and endocrine (cortisol) responses in adult male zebrafish. Overall, E2 exerted pro-social effect in the social preference test, reduced whole-body cortisol levels, elevated exploration in the novel tank test and increased the shoal size in the shoaling test, indicative of an anxiolytic-like profile of this hormone in male zebrafish. Supporting mounting human and rodent evidence on the role of E2 in behavioral regulation, the observed pro-social and anxiolytic-like effects of E2 in male zebrafish reinforce the use of this aquatic organism in studying steroid-mediated CNS mechanisms of complex affective and social behaviors.

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Melatonin is an important pineal hormone that regulates human and animal circadian rhythms and sleep. Mounting clinical and rodent evidence indicates that melatonin also modulates affective behaviors and cognition. The zebrafish (Danio rerio) is rapidly becoming a powerful novel model organism in translational neuroscience research. Here, we evaluate the effects of a 24-h melatonin treatment on behavior and physiology of adult zebrafish with circadian rhythm disturbed by a 24-h light exposure. While such light exposure evoked overt cognitive and neuroendocrine (cortisol) deficits in zebrafish, these effects were reversed by a 24-h melatonin treatment. Collectively, these findings suggest a positive modulation of affective and cognitive phenotypes in zebrafish by melatonin, and reinforce the growing utility of zebrafish models for studying circadian, cognitive and behavioral processes and their neuroendocrine regulation in vivo.

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Sex differences are an important variable in biomedical research. The zebrafish (Danio rerio) is rapidly becoming a critical novel model organism in translational neuroscience and neuropharmacology. Here, we examine the effects of sex on locomotor activity and anxiety-like behavior in adult zebrafish tested in the novel tank test following their exposure to two clinically relevant, common anxiolytic drugs diazepam and melatonin. While control female zebrafish were more active and anxious than males, both sexes showed anxiolytic responses to melatonin (0.232 mg/L) but only males responded to diazepam (16 µg/L). Revealing sex specificity in pharmacological responses, this study emphasizes the importance of sex differences in behavioral and pharmacological analyses in zebrafish. This may also be potentially relevant to modeling sex differences in clinical responses to anxiolytic drugs. Collectively, our data support sex differences in zebrafish behavioral responses and reinforce the growing utility of this aquatic model in CNS drug screening.

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Sex is an important variable in biomedical research. The zebrafish (Danio rerio) is increasingly utilized as a powerful new model organism in translational neuroscience and pharmacology. Mounting evidence indicates important sex differences in zebrafish behavioral and neuropharmacological responses. Here, we discuss the role of sex in zebrafish central nervous system (CNS) models, their molecular mechanisms, recent findings and the existing challenges in this field. We also emphasize the growing utility of zebrafish models in translational neuropharmacological research of sex differences, fostering future CNS drug discovery and the search for novel sex-specific therapies. Finally, we highlight the interplay between sex and environment in zebrafish models of sex-environment correlations as an important strategy of CNS disease modeling using this aquatic organism.

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Melatonin is an important hormone regulating circadian rhythm, neuroprotection and neuroimmune processes. However, its exact physiological roles in brain mechanisms remain poorly understood. Here, we summarize the mounting evidence implicating melatonin in brain disorders and behavior, based on clinical and experimental studies in-vivo. In addition to rodent models, the zebrafish (Danio rerio) is becoming increasingly utilized in biomedical and neuroscience research. Here, we discuss melatonin neurobiology of zebrafish, and parallel these findings with clinical and rodent data. We also discuss the genomic effects of melatonin in zebrafish, and emphasize the growing utility of zebrafish models to study melatonin neurobiology and drug discovery.

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The presence of endocrine-derived compounds in the environment occurs due to a myriad of human or industrial activity and can disrupt the endocrine system of animals, including fish. One important group of endocrine disruptors are the estrogens, such as 17-ß estradiol (E2, estradiol). Estrogens are gonadal steroid hormones, able to be influential even in small concentrations. Here, we demonstrate that E2 is linked to female' decisions made by an important coral reef species, the cleaner fish Labroides dimidiatus, during interactions with other reef fishes (known as clients). E2 treatment in natural conditions interfered directly in the cooperative relationships, by increasing cleaners' willingness to interact with clients, providing greater amounts of physical contact to their fish partners. We discuss the meaning of the observed behavioural disruption produced by E2, which by affecting a key species (cleaners) may produce a cascade impact in the aquatic ecosystem.

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We examined whether lithium carbonate (Li2CO3, 100mg/L) is able to prevent memory impairment induced by scopolamine. Moreover, we evaluated the effects of lithium on anxiety-like behavior and acetylcholinesterase activity in adult zebrafish. We demonstrated that lithium prevents the memory impairment induced by scopolamine, decreases exploration and increases the activity of acetylcholinesterase in zebrafish. Collectively, this contributes to a better understanding of the pharmacology of lithium, its interaction with cholinergic neurotransmission, and its possible application to therapeutic treatments aimed at improving cognition.

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Olfaction plays a key role in modulating behavioral and physiological responses of various animal species, including fishes. Olfactory deficits can be induced in fish experimentally, and utilized to examine the role of olfaction in their normal and pathological behaviors. Here, we examine whether experimental anosmia, evoked by ZnSO4 in adult zebrafish can be associated with behavioral and/or physiological responses. We show that experimental ZnSO4-induced anosmia caused acute, but not prolonged, anxiogenic-like effects on zebrafish behavior tested in the novel tank test. The procedure also elevated whole-body cortisol levels in zebrafish. Moreover, ZnSO4 treatment, but not sham, produced damage to olfactory epithelium, inducing overt basal cell vacuolization and intercellular edema. The loss of olfaction, assessed by the fish food preference behavior in the aquatic Y-maze, was present 1h, but not 24h, after the treatment. Collectively, this suggests that transient experimental anosmia by ZnSO4 modulates zebrafish behavior and olfaction, which can be used to evoke and assess their stress-related anxiety-like states.

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Jundiá (Rhamdia quelen) is a suitable species for aquaculture in regions of temperate or subtropical climate. This species has received great attention regarding several aspects of physiology as well as an organism to study the impact of environmental contaminations. However, experiments using validated and objective tests to evaluate the jundiá behavior are scarce. The effects of acute stress have been studied in other fish species, such as zebrafish (Danio rerio), however, the effects in jundiá are lacking. Thus, we evaluated the effects of acute stress (net chasing) on anxiety-like and social behavior in jundiá. For these purpose, all behavioral analyses were carried out using automated tracking software. We showed that the acute stress protocol increased cortisol levels and induced anxiogenic-like behavior in the novel tank test, and decreased social behavior in jundiá. The antidepressant fluoxetine was able to prevent the effects of acute stress on social behavior. Here we show a behavioral evaluation of Rhamdia quelen using consolidated tests and computerized analysis, which allows more measurable, reliable and comparable results.

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Olfaction is strongly involved in the regulation of fish behavior, including reproductive, defensive, social and migration behaviors. In fish, anosmia (the lack of olfaction) can be induced experimentally, impairing their ability to respond to various olfactory stimuli. Here, we examine the effects of experimental lidocaine-induced anosmia on anxiety-like behavior and whole-body cortisol levels in adult zebrafish (Danio rerio). We show that experimentally-induced anosmia reduces anxiolytic-like behavioral effects of fluoxetine and seems to interact with anxiogenic effect of stress also paralleling cortisol responses in zebrafish. These findings provide first experimental evidence that temporary anosmia modulates anxiety-like behaviors and physiology in adult zebrafish.

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