Adenosine A(2a) receptors are not confined to dopamine-rich areas of t
he brain, since thermocycling analysis shows that adenosine A(2a) rece
ptor mRNA is expressed also in the hippocampus (CA1, CA3 and dentate g
yrus) 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 ce
lls, 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 specif
ic binding sites in the hippocampus. The density of [H-3]CGS 21680 bin
ding 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 di
stribution 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) rec
eptor agonist, CPA, to inhibit neuronal activity was significantly att
enuated. These results show functionally important co-expression and c
o-localization of adenosine A(2a) and A(1) receptors in the hippocampu
s. The results also suggest that adenosine A(2a) receptor-mediated neu
romodulation is not confined to the basal ganglia, but is more widespr
ead throughout the nervous system.