Zebrafish Neuroscience Research Consortium

New Orleans, LA, United States

Zebrafish Neuroscience Research Consortium

New Orleans, LA, United States
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Maximino C.,Federal University of Pará | Maximino C.,Zebrafish Neuroscience Research Consortium | Araujo J.,Federal University of Pará | Araujo J.,Zebrafish Neuroscience Research Consortium | And 9 more authors.
Neurotoxicology and Teratology | Year: 2011

Adult zebrafish were treated acutely with methylmercury (1.0 or 5.0μgg -1, i.p.) and, 24h after treatment, were tested in two behavioral models of anxiety, the novel tank and the light/dark preference tests. At the smaller dose, methylmercury produced a marked anxiogenic profile in both tests, while the greater dose produced hyperlocomotion in the novel tank test. These effects were accompanied by a decrease in extracellular levels of serotonin, and an increase in extracellular levels of tryptamine-4,5-dione, a partially oxidized metabolite of serotonin. A marked increase in the formation of malondialdehyde, a marker of oxidative stress, accompanied these parameters. It is suggested that methylmercury-induced oxidative stress produced mitochondrial dysfunction and originated tryptamine-4,5-dione, which could have further inhibited tryptophan hydroxylase. These results underscore the importance of assessing acute, low-level neurobehavioral effects of methylmercury. © 2011 Elsevier Inc.


Maximino C.,Federal University of Pará | Maximino C.,Zebrafish Neuroscience Research Consortium | da Silva A.W.B.,Federal University of Pará | Gouveia A.,Federal University of Pará | And 2 more authors.
Progress in Neuro-Psychopharmacology and Biological Psychiatry | Year: 2011

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 (2. weeks), 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. © 2011 Elsevier Inc.


Maximino C.,Federal University of Pará | Maximino C.,Zebrafish Neuroscience Research Consortium | Lima M.G.,Federal University of Pará | Olivera K.R.M.,Federal University of Pará | And 3 more authors.
Basic and Clinical Pharmacology and Toxicology | Year: 2011

Adenosinergic systems have been implicated in anxiety-like states, as caffeine can induce a state of anxiety in human beings. Caffeine is an antagonist at A1 and A2 adenosine receptors but it remains unclear whether anxiety is mediated by one or both of these. As the adenosinergic system is rather conserved, we opted to pursue these questions using zebrafish, a widely used model organism in genetics and developmental biology. Zebrafish adenosine 1. 2A.1 and 2A.2 receptors conserve histidine residues in TM6 and TM7 that are responsible for affinity in bovine A1 receptor. We investigated the effects of caffeine, PACPX (an A1 receptor antagonist) and 1,3-dimethyl-1-propargylxanthine (DMPX) (an A2 receptor antagonist) on anxiety-like behaviour and locomotor activity of zebrafish in the scototaxis test as well as evaluated the effects of these drugs on pigment aggregation. Caffeine increased anxiety at the dose of 100mg/kg, while locomotion at the dose of 10mg/kg was increased. Both doses of 10 and 100mg/kg induced pigment aggregation. PACPX, on the other hand, increased anxiety at a dose of 6mg/kg and induced pigment aggregation at the doses of 0.6 and 6mg/kg, but did not produce a locomotor effect. DMPX, in turn, increased locomotion at the dose of 6mg/kg but did not produce any effect on pigment aggregation or anxiety-like behaviour. These results indicate that blockade of A1-R, but not A2-R, induces anxiety and autonomic arousal, while the blockade of A2-R induces hyperlocomotion. Thus, as in rodents, caffeine's anxiogenic and arousing effects are probably mediated by A1 receptors in zebrafish and its locomotor activating effect is probably mediated by A2 receptors. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.


Maximino C.,Federal University of Pará | Maximino C.,Zebrafish Neuroscience Research Consortium | Puty B.,Federal University of Pará | Benzecry R.,Federal University of Pará | And 7 more authors.
Neuropharmacology | Year: 2013

Serotonin (5-HT) is a neurotransmitter that is involved in many behavioral functions, including the organization of defense, and its putative pathological correlate, anxiety and stress disorders. Recently, behavioral tests for anxiety have been proposed in zebrafish. Exposure to the novel tank test or to the light/dark test increased extracellular fluid 5-HT content in the brain; anxiety-like behavior correlated positively with 5-HT content in the novel tank test, while the correlation was negative in the light/dark test. Acute treatment with a low dose of fluoxetine was anxiolytic in the geotaxis test and anxiogenic in the scototaxis test, while treatment with a higher dose produced a hyperlocomotor effect in both tasks. Buspirone and WAY 100635 were anxiolytic in both tests, while SB 224289 was anxiolytic in the geotaxis and slightly anxiogenic in the scototaxis test. Serotonin depletion with pCPA was anxiogenic in the geotaxis and anxiolytic in scototaxis. These results underline the differential sensitivity of these tasks to assess serotonergic agents; alternatively, serotonin might regulate zebrafish behavior differently in the novel tank test and in the light/dark test. © 2013 Elsevier Ltd. All rights reserved.


Maximino C.,Federal University of Pará | Maximino C.,Zebrafish Neuroscience Research Consortium | Lima M.G.,Federal University of Pará | Oliveira K.R.M.,Federal University of Pará | And 3 more authors.
Journal of Chemical Neuroanatomy | Year: 2013

The amygdaloid nuclei form an important hub of structures associated with diverse aspects of cognition and emotional behavior. Homologous structures have been determined in tetrapods, but homology of amygdala-like regions in bony fishes is presently unclear. Based on connectivity patterns, genoarchitecture, chemical neuroanatomy, and functional studies, we suggest that the dorsomedial portion of the pallium of Actinopterygii is the homolog of the basolateral/lateral amygdala (" frontotemporal amygdaloid system" ), while the supracommissural and postcommissural portions of the subpallium are homologous to the extended central amygdala (central amygdaloid nucleus and bed nucleus of the stria terminalis). Nonetheless, the differentiation between these nuclei is not as clear-cut as in mammals, and there is no clear evidence for the existence of an " olfactory" medial amygdala in Actinopterygii, suggesting that the parcellation of one or two amygdaloid nuclei into many subnuclei occurred with the appearance of a true vomeronasal system. © 2012 Elsevier B.V.


Maximino C.,Federal University of Pará | Maximino C.,Zebrafish Neuroscience Research Consortium | Benzecry R.,Federal University of Pará | Matos Oliveira K.R.,Federal University of Pará | And 10 more authors.
Behaviour | Year: 2012

The recent introduction of tasks to assess the behavior of zebrafish in novel and/or aversive environments has spurred great interest, prompting attempts to determine which constructs are modeled by these tasks (e.g., fear, anxiety, or some other construct). A review of the pharmacological and behavioral experiments indicates that not all behavioral testing models are equivalent. A more precise understanding of the parameters that influence task performance affords a wider selection of experimental procedures for investigating a particular construct, and also provides tools for differentiating the various constructs that may ultimately be of interest. In this review we will more closely examine two behavioral assays commonly used to measure the construct of 'anxiety' in adult zebrafish, with the conclusion that they do not both appear to be measuring a single underlying state. © 2012 Koninklijke Brill NV, Leiden.


Maximino C.,Pará State University | Maximino C.,Zebrafish Neuroscience Research Consortium | Gemaque J.,Federal University of Pará | Benzecry R.,Federal University of Pará | And 7 more authors.
Psychopharmacology | Year: 2015

Rationale: The adenosine A3 receptor and the nitric oxide (NO) pathway regulate the function and localization of serotonin transporters (SERTs). These transporters regulate extracellular serotonin levels, which are correlated with defensive behavior. Objective: The purpose of this study was to understand the role of the A3AR on anxiety and arousal models in zebrafish, and whether this role is mediated by the nitrergic modulation of serotonin uptake. Methods: The effects of IB-MECA (0.01 and 0.1 mg/kg) were assessed in a series of behavioral tasks in adult zebrafish, as well as on extracellular serotonin levels in vivo and serotonin uptake in brain homogenates. Finally, the interaction between IB-MECA and drugs blocking voltage-dependent calcium channels (VDCCs), NO synthase, and SERT was analyzed. Results: At the lowest dose, IB-MECA decreased bottom dwelling and scototaxis, while at the highest dose, it also decreased shoaling, startle probability, and melanophore responses. These effects were accompanied by an increase in brain extracellular serotonin levels. IB-MECA also concentration-dependently increased serotonin uptake in vitro. The effects of IB-MECA on extracellular 5-HT, scototaxis, and geotaxis were blocked by l-NAME, while only the effects on 5-HT and scototaxis were blocked by verapamil. In vitro, the increase in 5-HT uptake was dependent on VDCCs and NO. Finally, fluoxetine blocked the effect of IB-MECA on scototaxis, but not geotaxis. Conclusion: These results suggest that the effect of IB-MECA on scototaxis are mediated by a VDCC-NO-SERT pathway. While NO seems to mediate the effects of IB-MECA on geotaxis, neither VDCCs nor SERT seems to be involved in this process. © 2014 Springer-Verlag Berlin Heidelberg.


Maximino C.,University Estadual do Para | Maximino C.,Zebrafish Neuroscience Research Consortium | Puty B.,Federal University of Pará | Matos Oliveira K.R.,Federal University of Pará | And 2 more authors.
Genes, Brain and Behavior | Year: 2013

The zebrafish leopard phenotype (leo) displays abnormal pigmentation and shows increased anxiety-like behavior. The neurochemical changes associated with this anxious phenotype are not known. Here, we demonstrate that leo show increased anxiety-like behavior in the light/dark box and in the novel tank test. This anxious phenotype is rescued by acute treatment with a dose of a serotonin reuptake inhibitor, fluoxetine, that is inactive in wild-type animals. Moreover, leo show decreased tissue levels of serotonin, increased serotonin turnover and slightly increased monoamine oxidase activity. These results suggest that the anxious phenotype observed in leo zebrafish is caused by a decrease in serotonin uptake. This work could open an important avenue in defining the neurochemical underpinning of natural variation in anxiety disorders. Leopard zebrafish show a consistent increase in avoidant behavior in two models of anxiety that is associated with changes in serotonin transport and clearance.© 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.


Maximino C.,Federal University of Pará | Maximino C.,Zebrafish Neuroscience Research Consortium | Herculano A.M.,Federal University of Pará | Herculano A.M.,Zebrafish Neuroscience Research Consortium
Zebrafish | Year: 2010

Monoamine neurotransmitters are the major regulatory mechanisms in the vertebrate brain, involved in the adjustment of motivation, emotion, and cognition. The chemical anatomy of these systems is thought to be highly conserved in the brain of all vertebrates, including zebrafish. Recently, the development of behavioral assays in zebrafish allowed the neuropsychopharmacological investigation of these circuits and its functions. Here we review neuroanatomical, genetic, neurochemical, and psychopharmacological evidence regarding the roles of histaminergic, dopaminergic, noradrenergic, serotonergic, and melatonergic systems in this species. We conclude that, in spite of species differences, zebrafish are suitable for the investigation of neuropsychopharmacology of drugs that affect theses systems; nonetheless, more thorough validation of behavioral methods is still needed. © Copyright 2010, Mary Ann Liebert, Inc.

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