Role of nitric oxide in the behavioral and neurochemical effects of IB-MECA in zebrafish.
BACKGROUND
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.


CONCLUSIONS
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.
Laboratório de Neurociências e Comportamento, Universidade do Estado do Pará, Departamento de Morfologia e Ciências Fisiológicas, Núcleo Universitário de Marabá, Marabá, PA, Brazil, caio.maximino@gmail.com.
Caio
C
Maximino
Julliany
J
Gemaque
Rancés
R
Benzecry
Monica Gomes
MG
Lima
Evander de Jesus Oliveira
Ede J
Batista
Domingos Wanderley
DW
Picanço-Diniz
Karen Renata Matos
KR
Oliveira
Anderson Manoel
AM
Herculano
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015027:Zebrafish
D050486:Serotonin Plasma Membrane Transport Proteins; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D009569:Nitric Oxide; D012701:Serotonin; D019001:Nitric Oxide Synthase; D000241:Adenosine