Adenosine A(1) , but not A(2) , Receptor Blockade Increases Anxiety and Arousal in Zebrafish
- Authors
- Maximino, C., and Herculano, A.M.
- ID
- ZDB-PUB-110518-8
- Date
- 2011
- Source
- Basic & Clinical Pharmacology & Toxicology 109(3): 203-7 (Journal)
- Registered Authors
- Maximino, Caio
- Keywords
- none
- MeSH Terms
-
- Adenosine A1 Receptor Antagonists/pharmacology*
- Adenosine A2 Receptor Antagonists/pharmacology
- Animals
- Anxiety/chemically induced*
- Anxiety/metabolism
- Arousal/drug effects*
- Behavior, Animal/drug effects
- Caffeine/pharmacology*
- Cattle
- Darkness
- Dose-Response Relationship, Drug
- Melanophores/metabolism
- Mice
- Molecular Sequence Data
- Motor Activity/drug effects
- Pigments, Biological/metabolism
- Receptor, Adenosine A1/metabolism
- Receptor, Adenosine A1/physiology*
- Receptors, Adenosine A2/metabolism
- Receptors, Adenosine A2/physiology
- Sequence Alignment
- Zebrafish/metabolism*
- PubMed
- 21496211 Full text @ Basic Clin. Pharmacol. Toxicol.
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 which are responsible for affinity in bovine A1 receptor. We investigated the effects of caffeine, PACPX (an A1 receptor antagonist) and 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 100 mg kg-1, while locomotion at the dose of 10 mg kg-1 was increased. Both doses of 10 and 100 mg kg-1 induced pigment aggregation. PACPX, on the other hand, increased anxiety at a dose of 6 mg kg-1 and induced pigment aggregation at the doses of 0.6 and 6 mg kg-1, but did not produce a locomotor effect. DMPX, in turn, increased locomotion at the dose of 6 mg kg1 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.