A(1) AND A(2A) ADENOSINE RECEPTORS AND A(1) MESSENGER-RNA IN MOUSE-BRAIN - EFFECT OF LONG-TERM CAFFEINE TREATMENT

The effect of oral treatment with caffeine, in doses that are known to produce marked adaptive effects, was investigated on A(1) and A(2A) r eceptors in the mouse brain. Caffeine (0.1, 0.3 or 1 g/l) was added to the drinking water and the animals were sacrificed after a 14-day tre atment period. Ligand binding to A(1) receptors was studied, using qua ntitative autoradiography, with the agonist [H-3]cyclohexyladenosine ( CHA) and the antagonist [H-3]1,3-dipropyl-8-cyclopentyl xanthine (DPCP X). Caffeine did not remain in the sections during the autoradiography experiments. Caffeine treatment (1 g/l, but not 0.1 or 0.3 g/l) tende d to increase [H-3]CHA binding to the CA3 subfield of the hippocampus, but in no other region studied. There was no change in the number of A(1) receptors since [H-3]DPCPX binding to the CA3, cerebral and cereb ellar cortex was not influenced by caffeine treatment. There was simil arly no change in the ability of CHA to displace [H-3]DPCPX binding, s uggesting that there are no major changes in the proportion of A(1) re ceptors that are coupled to G-proteins. mRNA for the A(1) receptor, me asured by in situ hybridization, did not differ significantly between caffeine-treated and control mice in the structures examined. Thus, hi gher doses of caffeine can cause an increase in A(1) agonist binding w ithout a corresponding change in A(1) mRNA or in A(1) antagonist bindi ng, suggesting that the adaptive changes seen upon prolonged caffeine treatment may be in sites different from A(1) receptors. Caffeine (1 g /l) increased A(2A) receptors in the striatum measured as binding of t he agonist [H-3]CGS 21680 suggesting that up-regulation of A(2A) recep tors may be an adaptive effect of caffeine intake. (C) 1997 Elsevier S cience B.V.