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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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