Activation of central adenosine A(2A) receptors lowers the seizure threshold of hyperthermia-induced seizure in childhood rats

Abstract

Adenosine is a potent neuromodulator in the central nervous system (CNS). The functional deterioration of adenosine A(1) receptors in the CNS was reported to cause a failure of termination of seizures and to a lower seizure threshold of hyperthermia-induced seizures (HS) in childhood rats, which may contribute to adenosine-related convulsive disorders such as theophylline-associated seizures in childhood patients. In contrast to the inhibitory effect of adenosine A(1) receptors, the function of adenosine A(2A) receptors remains controversial. To clarify the function of adenosine A(2A) receptors in childhood convulsive disorders associated to hyperthermia, we investigated the in vivo interaction between adenosine A(2A) receptors and their ligands in HS in childhood rats. Adenosine selective A(2A) receptor ligands were injected intraperitoneally before HS. We measured brain temperature at the onset of seizures and the mortality rate after HS. We found that brain temperature at seizure onset was significantly higher in the A(2A) receptor antagonist group compared with that in the control group (p<0.05), and there was no significant difference in mortality among the groups. In contrast, brain temperature at seizure onset was significantly lower in the A(2A) receptor agonist group compared with that in the control group (p<0.05), and mortality was significantly higher in the A(2A) agonist group compared with that in the control group (p<0.001). The activation of the adenosine A(2A) receptor might enhance seizures associated to hyperthermia in the childhood human brain, and be involved in the pathogenesis of sudden unexpected death in epilepsy (SUDEP) in childhood patients with convulsive disorders.