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Abstract Depression is a wide-spread, debilitating psychiatric disorder. Mainly rodent-based, experimental animal models of depression are extensively used to probe the pathogenesis of this disorder. Here, we emphasize the need for innovative approaches to studying depression, and call for a wider use of novel model organisms, such as the zebrafish (Danio rerio), in this field. Highly homologous to humans and rodents, zebrafish are rapidly becoming a valuable tool in translational neuroscience research, but have only recently been utilized in depression research. Multiple conceptual and methodological problems, however, arise in relation to separating putative zebrafish depression-like states from motor and social deficits or anxiety. Here, we examine recent findings and the existing challenges in this field, to encourage further research and the use of zebrafish as novel organisms in cross-species depression modeling. [ABSTRACT FROM AUTHOR]

• Schizophrenia is an extremely debilitating lifelong psychiatric disorder. • It remains poorly understood, necessitating further translational research in this field. • Animal models are becoming a valuable tool to study schizophrenia. • Rodent models have been extensively used to target schizophrenia-related phenotypes and drugs. • Mounting evidence suggests zebrafish (Danio rerio) as a useful complementary tool to model schizophrenia. Schizophrenia is a severely debilitating, lifelong psychiatric disorder affecting approximately 1% of global population. The pathobiology of schizophrenia remains poorly understood, necessitating further translational research in this field. Experimental (animal) models are becoming indispensable for studying schizophrenia-related phenotypes and pro/antipsychotic drugs. Mounting evidence suggests the zebrafish (Danio rerio) as a useful tool to model various phenotypes relevant to schizophrenia. In addition to their complex robust behaviors, zebrafish possess high genetic and physiological homology to humans, and are also sensitive to drugs known to reduce or promote schizophrenia clinically. Here, we summarize findings on zebrafish application to modeling schizophrenia, as well as discuss recent progress and remaining challenges in this field. We also emphasize the need in further development and wider use of zebrafish models for schizophrenia to better understand its pathogenesis and enhance the search for new effective antipsychotics. [ABSTRACT FROM AUTHOR]

Abstract Despite the high prevalence of medicinal use and abuse of opioids, their neurobiology and mechanisms of action are not fully understood. Experimental (animal) models are critical for improving our understanding of opioid effects in vivo. As zebrafish (Danio rerio) are increasingly utilized as a powerful model organism in neuroscience research, mounting evidence suggests these fish as a useful tool to study opioid neurobiology. Here, we discuss the zebrafish opioid system with specific focus on opioid gene expression, existing genetic models, as well as its pharmacological and developmental regulation. As many human brain diseases involve pain and aberrant reward, we also summarize zebrafish models relevant to opioid regulation of pain and addiction, including evidence of functional interplay between the opioid system and central dopaminergic and other neurotransmitter mechanisms. Additionally, we critically evaluate the limitations of zebrafish models for translational opioid research and emphasize their developing utility for improving our understanding of evolutionarily conserved mechanisms of pain-related, addictive, affective and other behaviors, as well as for fostering opioid-related drug discovery. Highlights • Despite the growing use and abuse of opioids, their neurobiology is not fully understood. • Experimental models are critical for improving our understanding of opioid effects in vivo. • The zebrafish (Danio rerio) is becoming a powerful model organism in neuroscience research. • Here, we discuss the zebrafish opioid system and its genetic, genomic, pharmacological and behavioral regulation. • We emphasize the value of zebrafish for understanding opioid mechanisms and for CNS drug discovery. [ABSTRACT FROM AUTHOR]

Highlights • Aggression is a common agonistic behavior strongly affecting social life and wellbeing. • Zebrafish is rapidly becoming a new experimental model organism in neurobehavioral research. • Zebrafish present overt, easily quantifiable aggressive behaviors. • Here we discuss their utility in probing aggression neurobiology, genetics and environmental modulation. Abstract Aggression is a common agonistic behavior affecting social life and well-being of humans and animals. However, the underlying mechanisms of aggression remain poorly understood. For decades, studies of aggression have mostly focused on laboratory rodents. The growing importance of evolutionarily relevant, cross-species disease modeling necessitates novel model organisms to study aggression and its pathobiology. The zebrafish (Danio rerio) is rapidly becoming a new experimental model organism in neurobehavioral research. Zebrafish demonstrate high genetic and physiological homology with mammals, fully sequenced genome, ease of husbandry and testing, as well as rich, robust behavioral repertoire. As zebrafish present overt aggressive behaviors, here we focus on their behavioral models and discuss their utility in probing aggression neurobiology and its genetic, pharmacological and environmental modulation. We argue that zebrafish-based models represent an excellent translational tool to understand aggressive behaviors and related pathobiological brain mechanisms. [ABSTRACT FROM AUTHOR]

The endocannabinoid and opioid systems are two interplaying neurotransmitter systems that modulate drug abuse, anxiety, pain, cognition, neurogenesis and immune activity. Although they are involved in such critical functions, our understanding of endocannabinoid and opioid physiology remains limited, necessitating further studies, novel models and new model organisms in this field. Zebrafish ( Danio rerio ) is rapidly emerging as one of the most effective translational models in neuroscience and biological psychiatry. Due to their high physiological and genetic homology to humans, zebrafish may be effectively used to study the endocannabinoid and opioid systems. Here, we discuss current models used to target the endocannabinoid and opioid systems in zebrafish, and their potential use in future translational research and high-throughput drug screening. Emphasizing the high degree of conservation of the endocannabinoid and opioid systems in zebrafish and mammals, we suggest zebrafish as an excellent model organism to study these systems and to search for the new drugs and therapies targeting their evolutionarily conserved mechanisms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The adverse effects of mu opioid agonists have spurred a renewed interest in using kappa opioid receptor (KOR) agonists as analgesics. KOR agonists also have potential for development as diuretics for the treatment of edema and hypertension. Here, we evaluated the discriminative stimulus, antinociceptive, and diuretic effects of the kappa agonist (±)-trans-U-50488 and its stereoisomers (−)-(1 S ,2 S)-U-50488 or (+)-(1 R ,2 R)-U-50488) alone and in combination with the cannabinoid agonist (−)-CP 55,940. To establish (±)-U-50488 as a discriminative stimulus, rats (n = 12) were trained to discriminate intraperitoneal (i.p.) administration of 5.6 mg/kg of (±)-trans-U-50488 from saline under a fixed-ratio 20 (FR-20) schedule of food reinforcement. Then, antinociception was assessed using two procedures: warm water tail withdrawal and von Frey paw withdrawal. Diuretic effects were assessed in separate rats (n = 6/group). Doses of (±)-U-50488 and (−)-U-50488 that served as discriminative stimuli produced significant increases in urine output, but at lower doses than those that produced antinociception. In contrast, (+)-U-50488 alone had no discriminative stimulus or diuretic effects at the doses tested, but did produce antinociception in the von Frey assay. When three cannabinoids and morphine were tested in the (±)-U-50488 discrimination procedure to determine the similarity of these drugs' discriminative stimulus effects to those for (±)-U-50488, the rank order similarity was (−)-CP 55,940 > (−)-trans-THC > (+)-WIN 55,212–2 ≥ morphine. (−)-CP 55,940 alone (0.056 mg/kg) partially substituted for the discriminative stimulus effects of (±)-U-50488 and produced significant diuretic and antinociceptive effects. (−)-CP 55,940 in combination with (±)-U-50488 also produced a two-fold leftward shift in the discriminative stimulus curve for (±)-U-50488, and near-additive antinociception with (±)-U-50488 and (+)-U-50488. Further, the diuretic effect of (−)-CP 55,940 was enhanced by a dose of (+)-U50488, which itself did not alter urine output. These data together indicate that a combination of cannabinoid and kappa opioid agonists can enhance diuresis, but may have limited potential for serving as opioid-sparing pharmacotherapeutics for treatment of pain. • (±)-U-50488 and (-)-U-50488 had similar stimulus, diuretic, and antinociceptive effects. • CP 55,940 had subjective effects similar to those of (±)-U-50488. • CP 55.940 alone produced significant diuretic and antinociceptive effects. • The diuretic effects of CP 55,940 were enhanced by (+)-U-50488. [ABSTRACT FROM AUTHOR]