Biocultural psychopathology as a new epistemology for mental disorders.

Psychopathology has been criticized for decades for its reliance on a brain-centred and over-reductionist approach which views mental disorders as disease-like natural kinds. While criticisms of brain-centred psychopathologies abound, these criticisms sometimes ignore important advances in the neurosciences which view the brain as embodied, embedded, extended and enactive, and as fundamentally plastic. A new onto-epistemology for mental disorders is proposed, focusing on a biocultural model, in which human brains are understood as embodied and embedded in ecosocial niches, and with which individuals enact particular transactions characterized by circular causality. In this approach, neurobiological bases are inseparable from interpersonal and socio-cultural factors. This approach leads to methodological changes in how mental disorders are studied and dealt with.

Open Practical Laboratories in the Neurosciences: An outreach program for neuroscience communication in middle schools.

The Open Practical Laboratory in the Neurosciences is an outreach program that seeks to improve the knowledge of the neurosciences by elementary school students and to promote better attitudes in relation to neuroscience, science in general, and scientists. It consists in practical and demonstration activities on the theme of the neurosciences. This outreach strategy was applied in four public schools in a municipality in Southeastern Pará, Brazil characterized by low performance in educational reviews in Brazil. Students from both sexes from 9th grade (last grade before high school) were enrolled in the program. The outreach program improved students' knowledge about the neurosciences, and promoted better attitudes in relation to science and scientists, in comparison to students who did not go through the activities. Results suggest that scientific outreach strategies can produce results beyond immediate increases in knowledge, promoting better attitudes in relation to science.

Embryonic development of the fire-eye-tetra Moenkhausia oligolepis (Characiformes: Characidae).

This study describes the embryonic development of Moenkhausia oligolepis in laboratory conditions. After fertilization, the embryos were collected every 10 min up to 2 h, then every 20 min up to 4 h, and afterwards every 30 min until hatching. The fertilized eggs of M. oligolepis measured approximately 0.85 ± 0.5 mm and had an adhesive surface. Embryonic development lasted 14 h at 25ºC through the zygote, cleavage, blastula, gastrula, neurula, and segmentation phases. Hatching occurred in embryos around the 30-somites stage. The present results contribute only the second description of embryonic development to a species from the Moenkhausia genus, being also the first for this species. Such data are of paramount importance considering the current conflicting state of this genus phylogenetic classification and may help taxonomic studies. Understanding the biology of a species that is easily managed in laboratory conditions and has an ornamental appeal may assist studies in its reproduction to both supply the aquarium market and help the species conservation in nature. Moreover, these data enable the use of M. oligolepis as a model species in biotechnological applications, such as the germ cell transplantation approach.

Phasic and tonic serotonin modulate alarm reactions and post-exposure behavior in zebrafish.

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.

Emotional behavior in aquatic organisms? Lessons from crayfish and zebrafish.

Experimental animal models are a valuable tool to study the neurobiology of emotional behavior and mechanisms underlying human affective disorders. Mounting evidence suggests that various aquatic organisms, including both vertebrate (e.g., zebrafish) and invertebrate (e.g., crayfish) species, may be relevant to study animal emotional response and its deficits. Ideally, model organisms of disease should possess considerable genetic and physiological homology to mammals, display robust behavioral and physiological responses to stress, and should be sensitive to a wide range of drugs known to modulate stress and affective behaviors. Here, we summarize recent findings in the field of zebrafish- and crayfish-based tests of stress, anxiety, aggressiveness and social preference, and discuss further perspectives of using these novel model organisms in translational biological psychiatry. Outlining the remaining questions in this field, we also emphasize the need in further development and a wider use of crayfish and zebrafish models to study the pathogenesis of affective disorders.

Dopamine and serotonin mediate the impact of stress on cleaner fish cooperative behavior.

Stress is known to modulate behavioral responses and rapid decision-making processes, especially under challenging contexts which often occur in social and cooperative interactions. Here, we evaluated the effects of acute stress on cooperative behavior of the Indo-Pacific cleaner wrasse (Labroides dimidiatus) and the implications of pre-treatment with monoaminergic compounds: the selective serotonin reuptake inhibitor - fluoxetine, the 5-HT1A receptor antagonist - WAY-100,635, the D1 receptor agonist - SKF-38393, and the D1 receptor antagonist - SCH-23390. We demonstrated that stress decreased the predisposal to interact and increased cortisol levels in cleaners, which are alleviated by fluoxetine and the dopaminergic D1 antagonist. Overall, our findings highlight the crucial influence of stress on cooperative behavior.

A model to study orienting responses in zebrafish, and applications towards the emotion-cognition interaction.

Orienting responses (ORs) are whole-organism reflexes that are elicited by innocuous stimuli, and which decrease in magnitude after stimulus repetition. ORs represent relatively simple responses that can be used to study attentional processes, and are modulated by the organism's state, including arousal and activation levels, as well as by emotional processes. Here we describe a simple method to study ORs in zebrafish, a model organism increasingly being used in behavioural neuroscience. After presentation of a static visual stimulus, an OR is elicited, characterized by approaching the stimulus and orienting towards it. After repeated stimulation, OR decreases, suggesting habituation. These responses are qualitatively altered by exposure to a fear-eliciting alarm substance (i.e., derived from the skin of a conspecific), since exposed animals avoid the visual stimulus and orient either away from the stimulus or towards it, but at a distance. The protocol can be used to study orienting responses, as well as the impact of fear and arousal on these reflexes.

Reproductive cycle of the tetra Astyanax bimaculatus (Characiformes: Characidae) collected in Amazonian streams.

A histological characterization of gonadal development in the tetra Astyanax bimaculatus was performed, aimed at determining its reproductive cycle in streams localized inside the Amazonian forest. Collections were carried out monthly from August 2017 to July 2018 at the Zoobotânica Foundation of Marabá, PA. Collected specimens were weighed and measured, and their gonads and liver were removed and weighed to calculate gonadosomatic and hepatosomatic indexes. Gonads were fixed and treated for routine histology for light microscopy. Materials were stained with toluidine blue and haematoxylin and eosin. The Amazonian A. bimaculatus species presented two reproductive periods in the year, one at the end of the winter season and another during the summer. Females showed an asynchronous development of their oocytes and only two reproductive phases of development were observed during the whole period 'developing' and 'spawning capable'. Males presented cystic spermatogenesis, with an anastomosing tubular testis containing spermatogonia spread along the germinal epithelium (unrestricted spermatogonial). These morphological characteristics are considered phylogenetically more primitive. Male specimens were observed to have five different phases during the period: immature, initial maturation, mid maturation, final maturation and regression. The huge fluctuations in Amazonian streams was observed, in which water volumes varied considerably across seasons, culminating even in total drought. In spite of this, A. bimaculatus could be found during all seasons, showing its impressive reproductive adaptation to its conditions.

Seminal characterization of the Amazonian fire-eye tetra Moenkhausia oligolepis (Günther, 1864).

The seminal characteristics of Moenkhausia oligolepis are described. Three males were induced with a single dose of carp pituitary. Semen was collected 6 h after induction, and diluted in dibasic sodium phosphate extender solution. For motility analysis, 1 µl of diluted semen was added to 10 µl of distilled water to achieve gamete activation. The average duration of total motility was 76.67 s; while the average sperm motility rate at intervals of 15 s was 95.3, 85.3, 59.6, 31.7, 13.0, 4.6 and 1.2%. To determine sperm concentration in samples, 0.5 µl of semen was diluted with 500 µl of glutaraldehyde. An aliquot of 10 µl of this dilution was utilized for cell counting. An average count of 4.97 × 109 ± 3.46 sperm/ml was obtained. Morphological analyses were performed using eosin-nigrosine dye; 20.33% of the sperm were observed to be dead. Live sperm, comprising the other 79.67%, had an average length of approximately 30 µm, with a head diameter of 4.488 ± 0.7 µm; and a flagella plus mid-piece length of 26.071 ± 12.4 µm. Of those sperm, 69% had a normal morphology, while 31% had primary and secondary abnormalities. The observed abnormality rate did not have a detrimental effect on artificial fertilization potential for the species. The description of the seminal characteristics of a species is one of the most important sets of information required for artificial reproduction of fish in captivity. It also contributes significantly to the total biological knowledge of the studied species.

Behavioral models in psychopathology: epistemic and semantic considerations.

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.

Acute fluoxetine differently affects aggressive display in zebrafish phenotypes.

Zebrafish have been introduced as a model organism in behavioral neuroscience and biological psychiatry, increasing the breadth of findings using fish to study the neurobiology of aggression. Phenotypic differences between leopard and longfin zebrafish were exploited in order to elucidate the role of phasic serotonin in aggressive displays on this species. The present study, revealed differences in aggressive display between leopard and longfin zebrafish, and a discrepant effect of acute fluoxetine in both populations. In mirror-induced aggression, leopard animals showed higher display latencies than longfin, as well as lower display duration and frequency (Experiment 1). Moreover, 2.5 mg/kg fluoxetine decreased the duration and frequency of display in longfin, but not leopard; and 5 mg/kg fluoxetine increased display frequency in leopard, but not longfin (Experiment 2). It is suggested that zebrafish from the longfin phenotype show more aggressive motivation and readiness in the mirror-induced aggression test than leopard, and that acute fluoxetine increases aggression in leopard and decreased it in longfin zebrafish.

Sensory ecology of ostariophysan alarm substances.

Chemical communication of predation risk has evolved multiple times in fish species, with conspecific alarm substance (CAS) being the most well understood mechanism. CAS is released after epithelial damage, usually when prey fish are captured by a predator and elicits neurobehavioural adjustments in conspecifics which increase the probability of avoiding predation. As such, CAS is a partial predator stimulus, eliciting risk assessment-like and avoidance behaviours and disrupting the predation sequence. The present paper reviews the distribution and putative composition of CAS in fish and presents a model for the neural processing of these structures by the olfactory and the brain aversive systems. Applications of CAS in the behavioural neurosciences and neuropharmacology are also presented, exploiting the potential of model fish [e.g., zebrafish Danio rerio, guppies Poecilia reticulata, minnows Phoxinus phoxinus) in neurobehavioural research.

The integration of sociality, monoamines and stress neuroendocrinology in fish models: applications in the neurosciences.

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.

Mauritia flexuosa L. protects against deficits in memory acquisition and oxidative stress in rat hippocampus induced by methylmercury exposure.

OBJECTIVE: Methylmercury (MeHg) is the most toxic form of mercury that can affect humans through the food chain by bioaccumulation. Human organism is capable of triggering visual and cognitive disorders, neurodegeneration, as well as increased production of reactive species of O2 and depletion of natural anti-oxidant agents. In this context, Mauritia flexuosa L., a fruit rich in compounds with anti-oxidant properties, emerged as an important strategy to prevent the MeHg damages. So, this work has aimed to elucidate the protective effect of Mauritia flexuosa L. on the damage caused by the exposure of rats to MeHg. METHODS: In order to evaluate the effect of MeHg on rat aversive memory acquisition and panic-like behavior, we have used elevated T-maze apparatus and after behavioral test, the hippocampus was removed to perfom lipid peroxidation. RESULTS: Our results demonstrated that the exposure to MeHg caused deficits in inhibitory avoidance acquisition (aversive conditioning) and in the learning process, and increased levels of lipid peroxidation in hippocampus tissue. However, the pretreatment with feed enriched with Mauritia flexuosa L. showed a protective effect against cognitive deficits caused by MeHg and also prevented the occurrence of cytoplasmic membrane damage induced by lipid peroxidation in the hippocampal region. DISCUSSION: Therefore, this study suggests that Mauritia flexuosa L. represents an important strategy to prevent neurocytotoxics and behavioral effects of MeHg.

Nitric oxide as a regulatory molecule in the processing of the visual stimulus.

Nitric oxide (NO) is a highly reactive gas with considerable diffusion power that is produced pre- and post synaptically in the central nervous system (CNS). In the visual system, it is involved in the processing of the visual information from the retina to superior visual centers. In this review we discuss the main mechanisms through which nitric oxide acts, in physiological levels, on the retina, lateral geniculate nucleus (LGN) and primary visual cortex. In the retina, the cGMP-dependent nitric oxide activity initially amplifies the signal, subsequently increasing the inhibitory activity, suggesting that the signal is "filtered". In the thalamus, on dLGN, neuronal activity is amplified by NO derived from brainstem cholinergic cells, in a cGMP-independent mechanism; the result is the amplification of the signal arriving from retina. Finally, on the visual cortex (V1), NO acts through changes on the cGMP levels, increasing signal detection. These observations suggest that NO works like a filter, modulating the signal along the visual pathways.

Gametogenesis and seminatural reproduction of the Amazon twospot astyanax Astyanax bimaculatus (Linnaeus, 1758) cultivated in an enriched environment.

Environmental enrichment is used to provide well-being to the animals, such as fish, in captive conditions, mimicking their natural habitat. It may influence fish behavior, physiology, and survival. In terms of reproduction, however, the relationship between environment enrichment and successful reproduction in captivity is still poorly explored in fish species. Aiming to understand any possible benefits of structural enrichment on fish reproduction, 10-days-hatched larvae of the twospot astyanax Astyanax bimaculatus were raised for 18 weeks in tanks with different elements of structural environmental enrichment (PVC pipes, stones, and artificial plants). In the 5th month of life, those animals were hormonally induced to reproduce to assess gamete formation and offspring quality. Animals raised in a sterile-reared environment (non-enriched) showed earlier spawning than the enriched one, presenting significant quantities of Postovulatory follicle complexes (POCs) and cells in atresia in female ovaries, indicating possible reproductive dysfunction or stress, as well as a greater quantity of empty testicular lumen in males, indicating great release of sperm. On the contrary, animals cultivated in enriched environments showed gonads filled with semen in males and vitellogenic oocytes in females. Furthermore, offspring from the sterile-reared group presented significant rates of larval abnormality compared to the enriched group. In conclusion, the results of this study show that environmental enrichment can interfere with the reproduction of fish in captivity, mainly by preventing early maturation of gametes, which can result in low-quality offspring and, consequently, low production of fish species.

Activation of NOS-cGMP pathways promotes stress-induced sensitization of behavioral responses in zebrafish.

Nitric oxide (NO) is a molecule involved in plasticity across levels and systems. The role of NOergic pathways in stress-induced sensitization (SIS) of behavioral responses, in which a particular stressor triggers a state of hyper-responsiveness to other stressors after an incubation period, was assessed in adult zebrafish. In this model, adult zebrafish acutely exposed to a fear-inducing conspecific alarm substance (CAS) and left undisturbed for an incubation period show increased anxiety-like behavior 24 h after exposure. CAS increased forebrain glutamate immediately after stress and 30 min after stress, an effect that was accompanied by increased nitrite levels immediately after stress, 30 min after stress, 90 min after stress, and 24 h after stress. CAS also increased nitrite levels in the head kidney, where cortisol is produced in zebrafish. CAS-elicited nitrite responses in the forebrain 90 min (but not 30 min) after stress were prevented by a NOS-2 blocker. Blocking NOS-1 30 min after stress prevents SIS; blocking NOS-2 90 min after stress also prevents stress-induced sensitization, as does blocking calcium-activated potassium channels in this latter time window. Stress-induced sensitization is also prevented by blocking guanylate cyclase activation in both time windows, and cGMP-dependent channel activation in the second time window. These results suggest that different NO-related pathways converge at different time windows of the incubation period to induce stress-induced sensitization.

Social investigation and social novelty in zebrafish: Roles of salience and novelty.

Social preference tests can be used to analyze variables that influence and modify social behaviors, and to investigate effects of substances such as medications, drugs, and hormones. They may become important tools for finding a valid model to study neuropsychiatric changes and to study human neurodevelopmental processes that have been impaired by social events. While a preference for conspecifics has been shown for different species, social novelty has been used as a model for anxiety-like behavior in rodents. The goal of this research was to understand the roles of stimulus salience (numerousness) and novelty in social investigation and social novelty tests in zebrafish (Danio rerio Hamilton 1822). We used a sequential design, in which animals are exposed first to a social investigation test (with dichotomous presentation of novel conspecifics vs. empty tank) and then to a social novelty test (with dichotomous presentation of the already known conspecific and a novel conspecific). In experiment 1, animals were presented to either 1 or 3 (vs. an empty tank) conspecifics as stimuli. In experiment 2, animals were presented to 1 vs. 3 conspecifics as stimuli. In experiment 3, animals were observed in the social investigation and social novelty tests for 3 consecutive days. The results showed equivalence between 1 or 3 conspecifics in the social investigation and social novelty tests, although animals were able to discriminate between different shoal sizes. These preferences do not change with repeated test exposure, suggesting novelty to be a minor contributor to social investigation and social novelty in zebrafish.

Fish personality: meta-theoretical issues, personality dimensions, and applications to neuroscience and psychopathology.

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.

Oogenesis and in vitro reproduction of the twospot astyanax Astyanax bimaculatus (Linnaeus, 1758) exposed to conspecific alarm substance.

Stress situations can be essential to trigger reproduction in fish; however, it may also inhibit it. One of those situations involves the release of the conspecific alarm substance (CAS), a natural stressor, into the water by specific fish epidermal cells after a predator attack. Little is known about the effects of that substance on fish reproduction. This study aimed to evaluate the effects of CAS exposure on the oogenesis and reproduction of the twospot astyanax Astyanax bimaculatus before the hormonal induction for artificial reproduction. No macroscopic or cellular changes in the ovaries were observed for the females exposed to CAS, and the oocyte stages show all females in the same phase of maturation (Spawning Capable). Females exposed to CAS spawned 20 min before the females without exposure. On the other hand, they ovulated only once, whereas the females from the control group ovulated multiple times for approximately two hours after hormonal induction. Moreover, the precocious ovulation of the females submitted to CAS did not generate offspring, since all generated zygotes did not develop. In contrast, the control group females produced more than 11 thousand healthy larvae. Exposing the female fish to CAS during their reproductive management in captivity may reduce breeding success.