Dopamine denervation leads to an increase in the intramembrane interaction between adenosine A2 and dopamine D2 receptors in the neostriatum.

We have previously found, in striatal membrane preparations from young (2 months old) rats, that stimulation of adenosine A2 receptors (with the selective adenosine A2 agonist CGS 21680) increases the dissociation constants of high- (Kh) and low-affinity (Kl) dopamine D2 binding sites (labelled with the selective dopamine D2 antagonist [3H]raclopride) without changing the proportion of high affinity binding sites (Rh). In the present study in striatal preparations from adult (6 months old) rats, it was found that in addition to the increase in both Kh and Kl values, stimulation of adenosine A2 receptors is associated with an increase in Rh. These results suggest that, in the adult rat, adenosine A2 stimulation may inhibit the behavioural effects induced by dopamine D2 stimulation both by decreasing the affinity and the transduction of dopamine D2 receptors. We have also studied the intramembrane A2-D2 receptor interaction in an experimental model of Parkinson's disease, namely in rats with a unilateral 6-OH-dopamine-induced lesion of the nigro-striatal dopamine pathway. It was found that a unilateral dopamine denervation is associated with a higher density of striatal dopamine D2 receptors in the order of 20%, without any change in their affinity compared with the unlesioned neostriatum. Furthermore, the density (Bmax values) of dopamine D2 receptors in the contralateral neostriatum was significantly higher (about 20%) than in the striatum from naive animals. This finding suggests that an unilateral dopamine denervation also induces compensatory long-lasting changes of dopamine D2 receptors in the contralateral neostriatum.(ABSTRACT TRUNCATED AT 250 WORDS)