Adenosine is a well-known endogenous modulator of neuronal excitability with
anticonvulsant properties. Thus, the modulation exerted by
adenosine might be an effective tool to control
seizures. In this study, we investigated the effects of drugs that are able to modulate adenosinergic signaling on
pentylenetetrazole (PTZ)-induced
seizures in adult zebrafish. The
adenosine A1 receptor antagonist
8-cyclopentyl-1,3-dipropylxanthine (
DPCPX) decreased the latency to the onset of the tonic-clonic seizure stage. The
adenosine A1 receptor agonist cyclopentyladenosine (CPA) increased the latency to reach the tonic-clonic seizure stage. Both the
adenosine A2A receptor agonist and antagonist,
CGS 21680 and
ZM 241385, respectively, did not promote changes in seizure parameters. Pretreatment with the ecto-5'nucleotidase inhibitor
adenosine 5'-(α,β-methylene)
diphosphate (AMPCP) decreased the latency to the onset of the tonic-clonic seizure stage. However, when pretreated with the
adenosine deaminase (ADA) inhibitor, erythro-9-(2-hydroxy-3-nonyl)-adenine (
EHNA), or with the
nucleoside transporter (NT) inhibitors,
dipyridamole and S-(4-Nitrobenzyl)-6-thioinosine (
NBTI), animals showed longer latency to reach the tonic-clonic seizure status. Finally, our molecular analysis of the c-fos gene expression corroborates these behavioral results. Our findings indicate that the activation of
adenosine A1 receptors is an important mechanism to control the development of
seizures in zebrafish. Furthermore, the actions of
ecto-5'-nucleotidase, ADA, and NTs are directly involved in the control of extracellular
adenosine levels and have an important role in the development of seizure episodes in zebrafish.