EVIDENCE FOR FUNCTIONALLY IMPORTANT ADENOSINE A(2A) RECEPTORS IN THE RAT HIPPOCAMPUS

Adenosine A(2a) receptors are not confined to dopamine-rich areas of the brain, since thermocycling analysis shows that adenosine A(2a) receptor mRNA is expressed also in the hippocampus (CA1, CA3 and dentate gyrus) and cerebral cortex. The expression of A(2a) mRNA in three main areas of the hippocampus was confirmed by in situ hybridization; A(2a) mRNA expression was mainly localized in the pyramidal and granular cells, the same hippocampal regions that showed adenosine A(1) receptor mRNA expression. Receptor autoradiographic studies with [H-3]CGS 21680 (30 nM), a selective adenosine A(2a), receptor agonist, showed specific binding sites in the hippocampus. The density of [H-3]CGS 21680 binding was greatest in the stratum radiatum of the CA1 area, followed by the stratum oriens of the cornu Ammonis, stratum radiatum of the CA3 area and supra-granular layer of the dentate gyrus. This anatomical distribution of [H-3]CGS 21680 binding was similar to the pattern of [H-3]CHA binding in the hippocampus. Electrophysiological studies in the Schaffer fibers/CA1 pyramids showed that upon activation of the A(2a) receptors with CGS 21680 (10 nM) the ability of the adenosine A(1) receptor agonist, CPA, to inhibit neuronal activity was significantly attenuated. These results show functionally important co-expression and co-localization of adenosine A(2a) and A(1) receptors in the hippocampus. The results also suggest that adenosine A(2a) receptor-mediated neuromodulation is not confined to the basal ganglia, but is more widespread throughout the nervous system.