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Long‐term Effect of Convulsive Behavior on the Density of Adenosine A 1 and A 2A Receptors in the Rat Cerebral Cortex
Author(s) -
Rebola Nelson,
Porciúncula Lisiane O.,
Lopes Luísa V.,
Oliveira Catarina R.,
SoaresdaSilva Patrício,
Cunha Rodrigo A.
Publication year - 2005
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2005.01026.x
Subject(s) - kainate receptor , medicine , receptor , endocrinology , kindling , adenosine receptor , adenosine a1 receptor , chemistry , stimulation , kainic acid , long term depression , hippocampus , cerebral cortex , agonist , neuroscience , biology , glutamate receptor , ampa receptor
Summary: Purpose: Adenosine is a neuromodulator that has been proposed to act as an anticonvulsant mainly via inhibitory A 1 receptors, but recent data show that genetic deletion of facilitatory A 2A receptors might also attenuate convulsions. Since both A 1 and A 2A receptors are prone to down‐ and upregulation in different stressful situations, we investigated if convulsive behavior leads to a long‐term change in A 1 and A 2A 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 A 1 and A 2A receptor density in the cerebral cortex using both Western blot and membrane binding assays. Results: The binding density of the A 1 antagonist, 3 H‐DPCPX, decreased by 40. ± 4.4% and by 20.7 ± 0.5% after kindling or kainate injection. Likewise, A 1 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 A 2A receptor antagonist 3 H‐SCH 58261 increased by 293 ± 34% and by 159 ± 32% in cortical membranes from kindled or kainate‐injected rats, and A 2A 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 A 1 receptors accompanied by an increased density of A 2A receptors, suggesting that A 2A antagonists rather than A 1 agonists may be more promising anticonvulsive drugs.