Adenosine A2A receptor deficient mice are partially resistant to limbic seizures.
The neuromodulator adenosine, acting through activation of four defined metabotropic receptors called A(1), A(2A), A(2B) and A(3,) has been proposed as an endogenous anticonvulsant. Here, the consequences of deleting the adenosine A(2A) receptor have been examined in different experimental models of epilepsy. A(2A)R 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 A(2A) receptor knockout (A(2A)R KO) animals. A(2A)R KO mice exhibited reduced pentylenetetrazol-induced kindled seizures, demonstrating an important role of the A(2A) receptor in the acquisition of kindling. These data suggest that adenosine stimulating A(2A) receptors modulates excitatory neurotransmission and exacerbates limbic seizures. It is therefore suggested that adenosine A(2A) receptor antagonists might offer protection from some epileptic syndromes.
El Yacoubi
Malika
M
Unité de Neuropsychopharmacologie Expérimentale, F.R.E. 2735 Centre National de la Recherche Scientifique, I.F.R.M.P. 23, U.F.R. Médecine & Pharmacie, 22 Boulevard Gambetta, Rouen Cedex, France.
Ledent
Catherine
C
Parmentier
Marc
M
Costentin
Jean
J
Vaugeois
Jean-Marie
JM
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004597:Electroshock; D004827:Epilepsy / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010433:Pentylenetetrazole; D010862:Pilocarpine; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000209:etiology / Q000503:physiopathology*
D000927:Anticonvulsants; D043705:Receptor, Adenosine A2A; D010862:Pilocarpine; D000241:Adenosine; D010433:Pentylenetetrazole