Long-term Effect of Convulsive Behavior on the Density of Adenosine A1 and A2A Receptors in the Rat Cerebral Cortex

Abstract

Purpose: Adenosine is a neuromodulator that has been proposed to act as an anticonvulsant mainly via inhibitory A1 receptors, but recent data show that genetic deletion of facilitatory A2A receptors might also attenuate convulsions. Since both A1 and A2A receptors are prone to down- and upregulation in different stressful situations, we investigated if convulsive behavior leads to a long-term change in A1 and A2A receptor density in the rat cerebral cortex. Methods: Stage 4-5 convulsions (Racine's scale) were induced in adult Wistar rats either through amygdala stimulation (kindling) or by intraperitoneal injection of kainate (10 mg/ml). Rats were killed after 4 weeks to evaluate adenosine A1 and A2A receptor density in the cerebral cortex using both Western blot and membrane binding assays. Results: The binding density of the A1 antagonist, 3H-DPCPX, decreased by 40. ± 4.4% and by 20.7 ± 0.5% after kindling or kainate injection. Likewise, A1 receptor immunoreactivity in cortical membranes from kindled or kainate-injected rats decreased by 19.1 ± 3.3% and 12.7 ± 5.7%, respectively. In contrast, the binding density of the A2A receptor antagonist 3H-SCH 58261 increased by 293 ± 34% and by 159 ± 32% in cortical membranes from kindled or kainate-injected rats, and A2A receptor immunoreactivity also increased by 151 ± 12% and 79.6 ± 7.0%. Conclusions: This indicates that after convulsive behavior there is a long-term decrease of A1 receptors accompanied by an increased density of A2A receptors, suggesting that A2A antagonists rather than A1 agonists may be more promising anticonvulsive drugs.