ADENOSINE A(2A) RECEPTOR STIMULATION INCREASES RELEASE OF ACETYLCHOLINE FROM RAT HIPPOCAMPUS BUT NOT STRIATUM, AND DOES NOT AFFECT CATECHOLAMINE RELEASE

Rat striatal and hippocampal slices, preincubated with [H-3] dopamine (DA) {or [H-3] noradrenaline (NA)} and [C-14] choline, were superfused continuously and stimulated electrically. 2-chloroadenosine (2-CADO 0 .001-100 mu M), a non-selective adenosine receptor agonist, produced a concentration-dependent inhibition of the electrically evoked DA and acetylcholine (ACh) release from the striatal slices and of the electr ically evoked NA and ACh release from the hippocampal slices. 8-cyclop entyl-1,3-dipropylxanthine (DPCPX 3, 30 and 200 nM), a selective adeno sine A(1) receptor antagonist, caused a concentration-dependent, paral lel, rightward shift of the 2-CADO concentration-response curve, consi stent with competitive antagonism. The pA(2) values ranged between 8.4 and 8.8. In the case of ACh release from the hippocampus, but in no o ther case, was there an increase in release of radioactivity at low co ncentrations of 2-CADO in the presence of DPCPX. The stimulation in th e hippocampus could be blocked by a selective adenosine A(2A) receptor antagonist KF 17837. By itself KF 17837 (0.1-100 mu M) had no effect on electrically evoked NA release from hippocampal slices but decrease d electrically evoked ACh release. This inhibition was counteracted by DPCPX (1 mu M). These results show that under the conditions used, DA release in the striatum, and NA release in the hippocampus, as well a s ACh release from the striatum are regulated by adenosine A(1) but no t by adenosine A(1) receptors, which inhibit release, and by adenosine A(2A) receptors which stimulate release.