Understanding sex differences in zebrafish pain- and fear-related behaviors.

Sex is an important variable in translational biomedical research. While overt sex differences have been reported for pain and fear-like behaviors in humans and rodents, these differences in other popular model organisms, such as zebrafish, remain poorly understood. Here, we evaluate potential sex differences in zebrafish behavioral responses to pain (intraperitoneal administration of 5% acetic acid) and fear stimuli (exposure to alarm substance). Overall, both male and female zebrafish exposed to pain (acetic acid injection) show lesser distance traveled, fewer top entries and more writhing-like pain-related behavior vs. controls, whereas female fish more robustly (than males) altered some other pain-like behaviors (e.g., increasing freezing episodes and time in top) in this model. In contrast, zebrafish of both sexes responded equally strongly to fear evoked by acute alarm substance exposure. Collectively, these findings emphasize the growing importance of studying sex differences in zebrafish behavioral and pain models.

Sex differences shape zebrafish performance in a battery of anxiety tests and in response to acute scopolamine treatment.

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.

Putative anxiolytic-like behavioral effects of acute paracetamol in adult zebrafish.

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.

Color as an important biological variable in zebrafish models: Implications for translational neurobehavioral research.

Color is an important environmental factor that in multiple ways affects human and animal behavior and physiology. Widely used in neuroscience research, various experimental (animal) models may help improve our understanding of how different colors impact brain and behavioral processes. Complementing laboratory rodents, the zebrafish (Danio rerio) is rapidly emerging as an important novel model species to explore complex neurobehavioral processes. The growing utility of zebrafish in biomedicine makes it timely to consider the role of colors in their behavioral and physiological responses. Here, we summarize mounting evidence implicating colors as a critical variable in zebrafish models and neurobehavioral traits, with a particular relevance to CNS disease modeling, genetic and pharmacological modulation, as well as environmental enrichment and animal welfare. We also discuss the growing value of zebrafish models to study color neurobiology and color-related neurobehavioral phenomics, and outline future directions of research in this field.

The impact of housing environment color on zebrafish anxiety-like behavioral and physiological (cortisol) responses.

Color of the environment is an important factor modulating human and animal behavior and physiology. Animal models are a valuable tool to understand how colors affect social, cognitive and affective responses. The zebrafish (Danio rerio) is rapidly emerging as an important organism in neuroscience and physiology. Here, we examine whether the color of housing environment influences zebrafish anxiety-like behavior and whole-body cortisol levels. Overall, housing for 15 days in transparent and white holding tanks increases, and in black or blue tanks decreases, baseline anxiety-like behavior in adult zebrafish. Housing in blue tanks (vs. white) also reduced their whole-body cortisol levels. Taken together, our data suggest that color of the housing environment affects neurobehavioral and endocrine responses in zebrafish, with multiple implications for behavioral phenomics and animal welfare. Our study also reinforces zebrafish as a promising model organism to study neurobiology of compex brain-environment interactions.

Neuropharmacology, pharmacogenetics and pharmacogenomics of aggression: The zebrafish model.

The zebrafish (Danio rerio) is increasingly utilized as a powerful new model organism in neurobehavioral research. Aggression is a common symptom of many CNS disorders, has some genetic determinants and can be modulated pharmacologically in humans and animal model species. Mounting evidence suggests zebrafish as a useful tool to study neurobiology of aggression, and its pharmacological and genetic regulation. Here, we discuss mechanisms of zebrafish aggression and their pharmacological, pharmacogenetic and pharmacogenomic models, as well as recent developments and existing challenges in this field. We also emphasize the growing utility of zebrafish models in translational neuropharmacological research of aggression, fostering future discoveries of potential therapeutic agents for aggressive behavior.

The evolutionarily conserved role of melatonin in CNS disorders and behavioral regulation: Translational lessons from zebrafish.

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.

Effects of lidocaine on adult zebrafish behavior and brain acetylcholinesterase following peripheral and systemic administration.

Lidocaine is a voltage-gated Na+ channel blocker, commonly used as a fast-acting local and general anesthetic. Lidocaine also has central action, affecting behavior both clinically and in animal models. Adult zebrafish are rapidly becoming a critical novel model organism in translational neuroscience research. Here, we examine the effects of acute peripheral (lateral line application, 4%) and systemic (water immersion, 1, 5 and 10 mg/L) administration of lidocaine on adult zebrafish behavior tested in the novel tank test. Overall, the drug evoked hypolocomotor effect when applied systemically (at 10 mg/L) and peripherally. Peripheral lidocaine also reduced top exploration in the novel tank test (vs. sham), suggesting anxiogenic-like effect of the lateral line blockage, Our findings show the importance of the lateral line system in driving adult zebrafish locomotion, and suggest sedative-like effects of systemic lidocaine in aduld zebrafish. In addition, reflecting the role of central cholinergic contribution in lidocaine action, brain acetylcholinesterase (AChE) activity was lower following peripheral and systemic administration of lidocaine at behaviorally active doses. Collectively, our data support the effects of lidocaine on behavioral responses in zebrafish, and reinforce the growing utility of this aquatic model to screen various CNS drugs.

Psychoneuroimmunology and immunopsychiatry of zebrafish.

Despite the high prevalence of neural and immune disorders, their etiology and molecular mechanisms remain poorly understood. As the zebrafish (Danio rerio) is increasingly utilized as a powerful model organism in biomedical research, mounting evidence suggests these fish as a useful tool to study neural and immune mechanisms and their interplay. Here, we discuss zebrafish neuro-immune mechanisms and their pharmacological and genetic modulation, the effect of stress on cytokines, as well as relevant models of microbiota-brain interplay. As many human brain diseases are based on complex interplay between the neural and the immune system, here we discuss zebrafish models, as well as recent successes and challenges, in this rapidly expanding field. We particularly emphasize the growing utility of zebrafish models in translational immunopsychiatry research, as they improve our understanding of pathogenetic neuro-immune interactions, thereby fostering future discovery of potential therapeutic agents.