Due to the fish-specific genome duplication event (~320–350mya), some genes which code for serotonin proteins were duplicated in teleosts; this duplication event was preceded by a reorganization of ...the serotonergic system, with the appearance of the raphe nuclei (dependent on the isthmus organizer) and prosencephalic nuclei, including the paraventricular and pretectal complexes. With the appearance of amniotes, duplicated genes were lost, and the serotonergic system was reduced to a more complex raphe system. From a comparative point of view, then, the serotonergic system of zebrafish and that of mammals shows many important differences. However, many different behavioral functions of serotonin, as well as the effects of drugs which affect the serotonergic system, seem to be conserved among species. For example, in both zebrafish and rodents acute serotonin reuptake inhibitors (SSRIs) seem to increase anxiety-like behavior, while chronic SSRIs decrease it; drugs which act at the 5-HT1A receptor seem to decrease anxiety-like behavior in both zebrafish and rodents. In this article, we will expose this paradox, reviewing the chemical neuroanatomy of the zebrafish serotonergic system, followed by an analysis of the role of serotonin in zebrafish fear/anxiety, stress, aggression and the effects of psychedelic drugs.
•The 5-HTergic system of zebrafish is different from that of and mammals•5-HT modulation of anxiety-like behavior depends on the test used•5-HT acts at all levels of the hypothalamus-pituitary-interrenal axis•The 5-HT1A receptor tonically increases aggression•5-HTergic psychedelics produce a complex but predictable phenotype in zebrafish
Animal‐focused research has been crucial for scientific advancement, but rodents are still taking a starring role. Starting as merely supporting evidence found in rodents, the use of fish models has ...slowly taken a more central role and expanded its overall contributions in areas such as social sciences, evolution, physiology and recently in translational medical research. In the neurosciences, zebrafish Danio rerio have been widely adopted, contributing to our understanding of the genetic control of brain processes and the effects of pharmacological manipulations. However, discussion continues regarding the paradox of function versus structure, when fishes and mammals are compared and on the potentially evolutionarily conserved nature of behaviour across fish species. From a behavioural standpoint, we explore aversive–stress and social behaviour in selected fish models and refer to the extensive contributions of stress and monoaminergic systems. We suggest that, in spite of marked neuroanatomical differences between fishes and mammals, stress and sociality are conserved at the behavioural and molecular levels. We also suggest that stress and sociality are mediated by monoamines in predictable and non‐trivial ways and that monoamines could bridge the relationship between stress and social behaviour. To reconcile the level of divergence with the level of similarity, we need neuroanatomical, pharmacological, behavioural and ecological studies conducted in the laboratory and in nature. These areas need to add to each other to enhance our understanding of fish behaviour and ultimately how this all may lead to better model systems for translational studies.
Measuring anxiety in zebrafish: A critical review Maximino, Caio; de Brito, Thiago Marques; da Silva Batista, Annanda Waneza ...
Behavioural brain research,
2010-Dec-25, Letnik:
214, Številka:
2
Journal Article
Recenzirano
Zebrafish are increasingly being used in behavioral neuroscience, neuropsychopharmacology and neurotoxicology. Recently, behavioral screens used to model anxiety in rodents were adapted to this ...species, and novel models which tap on zebrafish behavioral ecology have emerged. However, model building is an arduous task in experimental psychopathology, and a continuous effort to assess the validity of these measurements is being chased among some researchers. To consider a model as valid, it must possess face, predictive and/or construct validity. In this article, we first review some notions of validity, arguing that, at its limit, face and predictive validity reduce to construct validity. Then we review some procedures which have been used to study anxiety, fear or related processes in zebrafish, using the validity framework. We conclude that, although the predictive validity of some of these models is increasingly being met, there is still a long way in reaching the desired level of construct validity. The refinement of models is an ongoing activity, and behavioral validation and parametric research ought to advance that objective.
Scototaxis as anxiety-like behavior in fish Maximino, Caio; Marques de Brito, Thiago; Dias, Claudio Alberto Gellis de Mattos ...
Nature protocols,
02/2010, Letnik:
5, Številka:
2
Journal Article
Recenzirano
The scototaxis (dark/light preference) protocol is a behavioral model for fish that is being validated to assess the antianxiety effects of pharmacological agents and the behavioral effects of toxic ...substances, and to investigate the (epi)genetic bases of anxiety-related behavior. Briefly, a fish is placed in a central compartment of a half-black, half-white tank; following habituation, the fish is allowed to explore the tank for 15 min; the number and duration of entries in each compartment (white or black) are recorded by the observer for the whole session. Zebrafish, goldfish, guppies and tilapias (all species that are important in behavioral neurosciences and neuroethology) have been shown to demonstrate a marked preference for the dark compartment. An increase in white compartment activity (duration and/or entries) should reflect antianxiety behavior, whereas an increase in dark compartment activity should reflect anxiety-promoting behavior. When individual animals are exposed to the apparatus on only one occasion, results can be obtained in 20 min per fish.
While the field of personality neuroscience has extensively focused on humans and, in a few cases, primates and rodents, a wide range of research on fish personality has emerged in the last decades. ...This research is focused mainly on the ecological and evolutionary causes of individual differences and also aimed less extensively at proximal mechanisms (e.g., neurochemistry or genetics). We argue that, if consistent and intentional work is made to solve some of the meta-theoretical issues of personality research both on fish and mammals, fish personality research can lead to important advances in personality neuroscience as a whole. The five dimensions of personality in fish (shyness-boldness, exploration-avoidance, activity, aggressiveness, and sociability) need to be translated into models that explicitly recognize the impacts of personality in psychopathology, synergizing research on fish as model organisms in experimental psychopathology, personality neuroscience, and ecological-ethological approaches to the evolutionary underpinnings of personality to produce a powerful framework to understand individual differences.
Evidence demonstrated that these fish retained visual memory of a familiar opponent for at least 5 days, but in other contexts (appetitive and aversive place conditioning) retention went beyond 15 ...days, which confirmed their ability to recognize, memorize, and change their behavioral response selectively in future encounters. Because interactions between individuals may vary in aggressiveness or stress, the outcome contributes to elicit an emotional state: for instance, the outcome of an agonist encounter is either becoming a winner or a loser (Oliveira et al., 2009), and, at the long term these encounters can lead to the formation of dominance hierarchies. The final article in the collection, by Ogawa and Parhar, reviews the role of a putative hub in the emotion-sociality interface, the habenula, in fish behavior, discussing the literature on the neuroanatomical organization of the habenula in mammals and fish, its behavioral functions, and convincingly arguing that this structure should be considered an interface between social behavior network and the mesolimbic reward system. ...given the role of the habenula in fear- and anxiety-like behavior, this structure is likely to also produce an interface with brain systems that are associated with defense (do Carmo Silva et al., 2018), thus representing an important cynosure that links stress, emotionality, and sociality (see Soares et al., 2018). Ogawa and Parhar also refers to the habenula as the target for the modulation of different neuropeptide and other neuroendocrine systems that are involved in the complex interactions between emotionality and sociality. ...the habenula and its projections to and from other structures in social, reward, and defensive systems are likely to play a crucial role in the social plasticity of emotion-like behavior in fish, as well as the effects of stress on sociality.
The use of animals in neurosciences has a long history. It is considered indispensable in areas in which "translational" research is deemed invaluable, such as behavioral pharmacology and comparative ...psychology. Animal models are being used in pharmacology and genetics to screen for treatment targets, and in the field of experimental psychopathology to understand the neurobehavioral underpinnings of a disorder and of its putative treatment. The centrality of behavioral models betrays the complexity of the epistemic and semantic considerations which are needed to understand what a model is. In this review, such considerations are made, and the breadth of model building and evaluation approaches is extended to include theoretical considerations on the etiology of mental disorders. This expansion is expected to help improve the validity of behavioral models and to increase their translational value. Moreover, the role of theory in improving construct validity creates the need for behavioral scientists to fully engage this process.
Current theories on the role of serotonin (5‐HT) in vertebrate defensive behavior suggest that this monoamine increases anxiety but decreases fear, by acting at different levels of the neuroaxis. ...This paradoxical, dual role of 5‐HT suggests that a serotonergic tone inhibits fear responses, while an acute increase in 5‐HT would produce anxiety‐like behavior. However, so far no evidence for a serotonergic tone has been found. Using zebrafish alarm responses, we investigate the participation of phasic and tonic 5‐HT levels in fear‐like behavior, as well as in behavior after stimulation. Conspecific alarm substance (CAS) increased bottom‐dwelling and erratic swimming, and animals transferred to a novel environment after CAS exposure (post‐exposure behavior) showed increased bottom‐dwelling and freezing. Clonazepam blocked CAS effects during and after exposure. Acute fluoxetine dose‐dependently decreased fear‐like behavior, but increased post‐exposure freezing. Metergoline had no effect on fear‐like behavior, but blocked the effects of CAS on post‐exposure behavior; similar effects were observed with para‐chlorophenylalanine. Finally, CAS was shown to decrease the activity of monoamine oxidase in the zebrafish brain after exposure. These results suggest that phasic and tonic serotonin encode an aversive expectation value, switching behavior toward cautious exploration/risk assessment/anxiety when the aversive stimulus is no longer present.
Hypothetical mechanism of the serotonergic signaling in zebrafish defensive behavior during and after exposure to conspecific alarm substance (CAS). CAS elicits responses dominated by erratic swimming, which decreases as the substance's concentrations decline. After CAS exposure, the behavioral response is dominated by freezing. Serotonin (5‐HT) shifts responding from the first to the second (represented by the purple arrow, as well as by the arrows connecting the raphe to the “switch” green boxes), putatively by switching control from the mesencephalic aversive circuit (“switch OFF”) to the prosencephalic aversive circuit (“switch ON”).
The scototaxis test has been introduced recently to assess anxiety-like phenotypes in fish, including zebrafish. Parametric analyses suggest that scototaxis represents an approach–avoidance conflict, ...which hints at anxiety. In this model, white avoidance represents anxiety-like behavior, while the number of shuttling events represents activity. Acute or chronic fluoxetine, buspirone, benzodiazepines, ethanol, caffeine and dizocilpine were assessed using the light–dark box (scototaxis) test in zebrafish. Acute fluoxetine treatment did not alter white avoidance, but altered locomotion in the higher dose; chronic treatment (2weeks), on the other hand, produced an anxiolytic effect with no locomotor outcomes. The benzodiazepines produced a hormetic (inverted U-shaped) dose–response profile, with intermediate doses producing anxiolysis and no effect at higher doses; clonazepam, a high-potency benzodiazepine agonist, produced a locomotor impairment at the highest dose. Buspirone produced an anxiolytic profile, without locomotor impairments. Moclobemide did not produce behavioral effects. Ethanol also produced a hormetic profile in white avoidance, with locomotor activation in 0.5% concentration. Caffeine produced an anxiogenic profile, without locomotor effects. These results suggest that the light–dark box is sensitive to anxiolytic and anxiogenic drugs in zebrafish.
► Preference for dark environments is thought to represent anxiety in zebrafish. ► Chronic, but not acute, fluoxetine had an anxiolytic effect in scototaxis. ► Buspirone had the same effect, but moclobemide did not. ► Benzodiazepines also were anxiolytic in smaller doses, and ataxic at higher doses. ► Ethanol was anxiolytic at the smallest dose, but motor-activating at higher doses.
The tectum is a structure localized in the roof of the midbrain in vertebrates, and is taken to be highly conserved in evolution. The present article assessed three hypotheses concerning the ...evolution of lamination and citoarchitecture of the tectum of nontetrapod animals: 1) There is a significant degree of phylogenetic inertia in both traits studied (number of cellular layers and number of cell classes in tectum); 2) Both traits are positively correlated accross evolution after correction for phylogeny; and 3) Different developmental pathways should generate different patterns of lamination and cytoarchitecture.
The hypotheses were tested using analytical-computational tools for phylogenetic hypothesis testing. Both traits presented a considerably large phylogenetic signal and were positively associated. However, no difference was found between two clades classified as per the general developmental pathways of their brains.
The evidence amassed points to more variation in the tectum than would be expected by phylogeny in three species from the taxa analysed; this variation is not better explained by differences in the main course of development, as would be predicted by the developmental clade hypothesis. Those findings shed new light on the evolution of an functionally important structure in nontetrapods, the most basal radiations of vertebrates.
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