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.

Pro-social and anxiolytic-like behavior following a single 24-h exposure to 17ß-estradiol in adult male zebrafish.

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.

An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish.

BACKGROUND: A potent acetylcholinesterase inhibitor, donepezil is a cognitive enhancer clinically used to treat neurodegenerative diseases. However, its complete pharmacological profile beyond cognition remains unclear. The zebrafish (Danio rerio) is rapidly becoming a powerful novel model organism in neuroscience and central nervous system drug screening. AIM: Here, we characterize the effects of 24-h donepezil administration on anxiety-like behavioral and endocrine responses in adult zebrafish. METHODS: We evaluated zebrafish anxiety-like behaviors in the novel tank, the light-dark and the shoaling tests, paralleled by assessing brain acetylcholinesterase activity and whole-body cortisol levels. RESULTS: Overall, donepezil dose-dependently decreased zebrafish locomotor activity in the novel tank test and reduced time in light in the light-dark test, likely representing hypolocomotion and anxiety-like behaviors. Donepezil predictably decreased brain acetylcholinesterase activity, also increasing whole-body cortisol levels, thus further linking acetylcholinesterase inhibition to anxiety-like behavioral and endocrine responses. CONCLUSION: Collectively, these findings suggest negative modulation of zebrafish affective behavior by donepezil, support the key role of cholinergic mechanisms in behavioral regulation in zebrafish, and reinforce the growing utility of zebrafish models for studying complex behavioral processess and their neuroendocrine and neurochemical regulation.

Zebrafish models of impulsivity and impulse control disorders.

Impulse control disorders (ICDs) are characterized by generalized difficulty controlling emotions and behaviors. ICDs are a broad group of the central nervous system (CNS) disorders including conduct disorder, intermittent explosive, oppositional-defiant disorder, antisocial personality disorder, kleptomania, pyromania and other illnesses. Although they all share a common feature (aberrant impulsivity), their pathobiology is complex and poorly understood. There are also currently no ICD-specific therapies to treat these illnesses. Animal models are a valuable tool for studying ICD pathobiology and potential therapies. The zebrafish (Danio rerio) has become a useful model organism to study CNS disorders due to high genetic and physiological homology to mammals, and sensitivity to various pharmacological and genetic manipulations. Here, we summarize experimental models of impulsivity and ICD in zebrafish and highlight their growing translational significance. We also emphasize the need for further development of zebrafish ICD models to improve our understanding of their pathogenesis and to search for novel therapeutic treatments.

Melatonin treatment reverses cognitive and endocrine deficits evoked by a 24-h light exposure in adult zebrafish.

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.