ANTAGONISTIC A2A/D2 RECEPTOR INTERACTIONS IN THE STRIATUM AS A BASIS FOR ADENOSINE/DOPAMINE INTERACTIONS IN THE CENTRAL-NERVOUS-SYSTEM

From behavioural and biochemical experiments, we have found evidence for the existence of a specific adenosine A2a receptor/dopamine D2 receptor interaction in the brain. Behavioural data show that stimulation of A2a receptors inhibits and their blockade potentiates a D2-mediated locomotor activation in mice and that stimulation of D2 receptors counteracts on A2a-mediated cataleptic effect in rats. Biochemical data show that, in rat striatal membrane preparations, A2a receptor stimulation decreases the affinity of D2 receptors and the transduction of the signal from the D2 receptor to the G-protein. Based on these findings it is postulated that this A2a/D2 interaction might be the main mechanism responsible for the central effects of adenosine agonists and antagonists, like methylxanthines. The increased behavioural effect of methylxanthines after dopamine denervation could be explained by an increased interaction between adenosine A2a and dopamine D2 receptors. Membrane preparations from dopamine-denervated striatum are more sensitive to the effect of adenosine A2a receptor stimulation. Our results underline the potential antiparkinsonian action of adenosine A2a antagonists and the potential antipsychotic action of adenosine A2a agonists.