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 subtypes were determined using in vivo microdialysis in an attempt to elucidate their different psychotropic mechanisms of action. Adenosine and a selective adenosine A(1) receptor agonist decreased the striatal extracellular dopamine level, whereas caffeine, carbamazepine and a selective adenosine A(1) receptor antagonist increased it, but neither an adenosine A(2) receptor agonist nor an antagonist affected it. Under conditions 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 adenosine 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 conditions of adenosine A(1) receptor blockade increases it. Therefore, caffeine is an antagonist of both adenosine A(1) and A(2) receptor subtypes, and carbamazepine is an adenosine A(1) receptor antagonist as well as an adenosine A(2) receptor agonist. These properties support the hypothesis that the central actions of both carbamazepine and caffeine result from effects on both adenosine A(1) and A(2) receptors.