Modification of adenosine A1 and A2A receptor density in the hippocampus of streptozotocin-induced diabetic rats

Adenosine A1 and A2A receptors are neuromodulatory systems that can control mnemonic behavior, which is modified by diabetes. Since the density of these adenosine receptors can change upon chronic noxious brain conditions, we now tested if the density of A1 and A2A receptors was modified in the hippocampus of streptozotocin-induced diabetic rats. The binding density of the selective A1 receptor antagonist, 3H-DPCPX, was decreased by 36% in total hippocampal membranes 7 days after induction of diabetes and this down-regulation was maintained after 30 and 90 days, which was also confirmed by Western blot analysis of A1 receptor immunoreactivity. In contrast, the binding density of the selective A2A receptor antagonist, 3H-SCH 58261, was enhanced by 83% in total hippocampal membranes 7 days after induction of diabetes and this up-regulation persisted after 30 and 90 days. These results show that the balance between inhibitory A1 and facilitatory A2A adenosine receptors is modified in the hippocampus of streptozotocin-induced diabetic rats. Thus, the most abundant A1 receptors are down-regulated and there is an up-regulation of A2A receptors, suggesting a gain of function of hippocampal A2A receptors compared to A1 receptors in diabetes, as has been observed in other chronic noxious brain conditions where A2A receptor blockade affords robust neuroprotection.