Seizure suppression by adenosine A 2A receptor activation in a rat model of audiogenic brainstem epilepsy

Abstract

Adenosine is known to suppress seizure activity mainly by activation of adenosine A 1 receptors. However, little is known about the potential involvement of other types of adenosine receptors in seizure suppression. It was now tested whether activation of adenosine A 2A receptors would be effective in the suppression of generalized brainstem seizures. Genetically epilepsy-prone rats were intraperitoneally injected with increasing doses of the A 2A receptor agonist, 5′-( N-cyclopropyl)-carboxamido-adenosine (CPCA), and, for comparison, with the A 1 receptor agonist, 2-chloro- N 6-cyclopentyladenosine (CCPA). Both CPCA and CCPA were effective in suppressing generalized brainstem seizures with minimal effective concentrations of 2.5 and 1.5 mg/kg, respectively. Seizure suppression was maintained when CPCA was co-injected with the peripherally acting adenosine receptor antagonist 8-( p-sulphophenyl)theophylline, suggesting that central activation of A 2A receptors effectively contributes to seizure suppression.