DETERMINATION OF THE EFFECTS OF CAFFEINE AND CARBAMAZEPINE ON STRIATAL DOPAMINE RELEASE BY IN-VIVO MICRODIALYSIS

The effects of carbamazepine and caffeine on adenosine receptor subtyp es were determined using in vivo microdialysis in an attempt to elucid ate their different psychotropic mechanisms of action. Adenosine and a selective adenosine A(1) receptor agonist decreased the striatal extr acellular dopamine level, whereas caffeine, carbamazepine and a select ive adenosine A(1) receptor antagonist increased it, but neither an ad enosine A(2) receptor agonist nor an antagonist affected it. Under con ditions of adenosine A(1) receptor blockade, adenosine, carbamazepine and a selective adenosine A(2) receptor agonist increased the striatal extracellular dopamine level, whereas caffeine and a selective adenos ine A(2) receptor antagonist decreased it. These results suggest that adenosine A(1) receptor stimulation reduces the striatal extracellular dopamine level, and that adenosine A(2) receptor stimulation under co nditions of adenosine A(1) receptor blockade increases it. Therefore, caffeine is an antagonist of both adenosine A(1) and A(2) receptor sub types, and carbamazepine is an adenosine A(1) receptor antagonist as w ell as an adenosine A(2) receptor agonist. These properties support th e hypothesis that the central actions of both carbamazepine and caffei ne result from effects on both adenosine A(1) and A(2) receptors.