EXCITATORY AND INHIBITORY EFFECTS OF A(1) AND A(2A) ADENOSINE RECEPTOR ACTIVATION ON THE ELECTRICALLY-EVOKED [H-3] ACETYLCHOLINE-RELEASE FROM DIFFERENT AREAS OF THE RAT HIPPOCAMPUS

The modulation by adenosine analogues and endogenous adenosine of the electrically evoked release of [H-3]acetylcholine ([H-3]ACh) was compa red in subslices of the three areas of the rat hippocampus (CA1, CA3, and dentate gyrus). The mixed A(1)/A(2) agonist 2-chloroadenosine (CAD O; 2-10 mu M) inhibited, in a concentration-dependent manner, the rele ase of [H-3]ACh from the three hippocampal areas, being more potent in the CA1 and CA3 areas than in the dentate gyrus. The inhibitory effec t of CADO (5 mu M) on [H-3]ACh release was prevented by the A(1) antag onist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 50 nM) in the three h ippocampal areas and was converted in an excitatory effect in the CA3 and dentate gyrus areas. The A(2A) agonist CGS-21630 (30 nM) produced a greater increase of the evoked release of [H-3]ACh in the CA3 than i n the dentate gyrus areas, whereas no consistent effect was found in t he CA1 area or in the whole hippocampal slice. The excitatory effect o f CGS-21680 (30 nM) in the CA3 area was prevented by the adenosine rec eptor antagonist 3,7-dimethyl-1-propargylxanthine (10 mu M). Both aden osine deaminase (2 U/ml) and DPCPX (250 nM) increased the evoked relea se of [H-3]ACh in the CA1 and CA3 areas but not in the dentate gyrus. The amplitude of the effect of DPCPX and adenosine deaminase was simil ar in the CA1 area, but in the CA3 area DPCPX produced a greater effec t than adenosine deaminase. It is concluded that the electrically evok ed release of [H-3]ACh in the three areas of the rat hippocampus can b e differentially modulated by adenosine. In the CA1 area, only A(1) in hibitory receptors modulate ACh release, whereas in the CA3 area, both A(2A) excitatory and A(1) inhibitory adenosine receptors modulate ACh release. In the dentate gyrus, both A(1) inhibitory and A(2A) excitat ory adenosine receptors are present, but endogenous adenosine does not activate them.