A 1 and A 2A adenosine receptors and A 1 mRNA in mouse brain: effect of long-term caffeine treatment

Abstract

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 receptors 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 treatment period. Ligand binding to A 1 receptors was studied, using quantitative autoradiography, with the agonist [ 3H]cyclohexyladenosine (CHA) and the antagonist [ 3H]1,3-dipropyl-8-cyclopentyl xanthine (DPCPX). 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) tended to increase [ 3H]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 [ 3H]DPCPX binding to the CA3, cerebral and cerebellar cortex was not influenced by caffeine treatment. There was similarly no change in the ability of CHA to displace [ 3H]DPCPX binding, suggesting that there are no major changes in the proportion of A 1 receptors that are coupled to G-proteins. mRNA for the A 1 receptor, measured by in situ hybridization, did not differ significantly between caffeine-treated and control mice in the structures examined. Thus, higher doses of caffeine can cause an increase in A 1 agonist binding without a corresponding change in A 1 mRNA or in A 1 antagonist binding, 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 the agonist [ 3H]CGS 21680 suggesting that up-regulation of A 2A receptors may be an adaptive effect of caffeine intake.