Medium- and long-term alterations of brain A 1 and A 2A adenosine receptor characteristics following repeated seizures in developing rats

Abstract

In order to assess long-lasting consequences of recurrent seizures during development, the effects of repeated seizures in developing rats were investigated on brain adenosine A 1 and A 2A receptors. The characteristics of A 1 and A 2A receptors were analyzed by measuring the binding of the selective agonists [ 3H]CHA ( N 6-cyclohexyladenosine) and [ 3H]CGS 21680 (2-[ p-(2-carboxyethyl)-phenethylamino]-5′- N-ethylcarboxamido adenosine), respectively, on cerebral membrane preparations, whereas receptor coupling to G-proteins was examined by using a GTP analogue (Gpp(NH)p; guanylyl-5′-imidodiphosphate). Seizures were induced by bicuculline once a day at two different developmental stages: either from postnatal day 5 to postnatal day 7 (P5–P7) or from P15 to P17. Adenosine receptors were then studied at P15, P25 and P60. P5–P7 seizures led to an increase in A 1 receptor density at P60 and to a decrease in their coupling to G-proteins at P15, but they did not affect A 2A receptors. P15–P17 seizures decreased the coupling of A 1 receptors to G-proteins at P25 and P60, reduced the density of A 2A receptors at P25 and increased their affinity at P60. These results depict a persistent sensitivity of both A 1 and A 2A brain adenosine receptors to repeated seizures, with selective receptor alterations according to the cerebral maturational stage when seizures occur. In respect to the neuromodulatory and anticonvulsant properties of adenosine, such changes might be implicated in long-term functional brain reorganization after early seizures and future susceptibility to convulsive disorders.