Adenosine A2A receptor deficient mice are partially resistant to limbic seizures

The neuromodulator adenosine, acting through activation of four defined metabotropic receptors called A1, A2A, A2B and A3, has been proposed as an endogenous anticonvulsant. Here, the consequences of deleting the adenosine A2A receptor have been examined in different experimental models of epilepsy. A2AR KO mice were not protected against seizures originating from brainstem structures, namely electroshock-induced seizures. The intensities of seizures induced by pentylenetetrazol or pilocarpine, as well as the percentages of convulsing mice, were significantly reduced in A2A receptor knockout (A2AR KO) animals. A2AR KO mice exhibited reduced pentylenetetrazol-induced kindled seizures, demonstrating an important role of the A2A receptor in the acquisition of kindling. These data suggest that adenosine stimulating A2A receptors modulates excitatory neurotransmission and exacerbates limbic seizures. It is therefore suggested that adenosine A2A receptor antagonists might offer protection from some epileptic syndromes.