Recent pharmacological data suggest that a receptor-receptor interaction between adenosine A2 and dopamine D2 receptors in the brain underlies the behavioral effects of adenosine agonists and adenosine antagonists, such as caffeine and theophylline. According to this interaction, stimulation of A2 receptors inhibits and their blockade potentiates the effects of D2 receptor stimulation. Furthermore, both A2 and D2 receptors are selectively colocalized on GABAergic striopallidal neurons. In this microdialysis investigation the effect of intrastriatal infusion of adenosine and dopamine agonists and antagonists alone or in combination was studied on the release of GABA from the terminals of the striopallidal neuron in awake, freely moving rats. We report that the GABAergic striopallidal neuron, which is a key component of the indirect striatal efferent pathway, is a main locus for A2-D2 interactions in the brain and possibly a main target for the central actions of adenosine agonists and antagonists.