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A1 and A2A adenosine receptors and A1 mRNA in mouse brain: effect of long-term caffeine treatment

1997; Elsevier BV; Volume: 762; Issue: 1-2 Linguagem: Inglês

10.1016/s0006-8993(97)00378-8

1872-6240

Björn Johansson, Vasil Georgiev, Karin Lindström, Bertil B. Fredholm,

Neuroscience and Neuropharmacology Research

The effect of oral treatment with caffeine, in doses that are known to produce marked adaptive effects, was investigated on A1 and A2A 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 A1 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 A1 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 A1 receptors that are coupled to G-proteins. mRNA for the A1 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 A1 agonist binding without a corresponding change in A1 mRNA or in A1 antagonist binding, suggesting that the adaptive changes seen upon prolonged caffeine treatment may be in sites different from A1 receptors. Caffeine (1 g/l) increased A2A receptors in the striatum measured as binding of the agonist [3H]CGS 21680 suggesting that up-regulation of A2A receptors may be an adaptive effect of caffeine intake.