Adenosine A(2A) and group I metabotropic glutamate receptors synergistically modulate the binding characteristics of dopamine D-2 receptors in the rat striatum

There is experimental evidence for the existence of interactions between me tabotropic glutamate (mGlu), adenosine and dopamine receptors in the striat um. In membrane preparations from rat striatum the group I and II mGlu rece ptor agonist 1-aminocyclopentane-1S-3R-dicarboxylic acid (1S-3R-ACPD) was f ound to modulate the binding characteristics of D-2 receptors in a similar manner as the A(2A) receptor agonist 2-[p-(2-carboxyethyl)phenthylamino]-5' -N-ethylcarboxamidoadenosine (CGS 21680), with a significant decrease in th e affinity of the high-affinity state of D-2 receptors for dopamine. The ef fect of 1S-3R-ACPD was mimicked by (+/-)-trans-ACPD (t-ACPD; a racemic mixt ure of 1S-3R-ACPD and its inactive isomer 1R-3S-ACPD) and by the selective group I mGlu receptor agonist 3,5-dihydroxyphenylglycine (DHPG) and it was counteracted by the selective group I mGlu receptor antagonist 1-aminoindan -1,5-dicarboxilic acid (AIDA), but not by the the group II and III mGlu rec eptor antagonist (RS)-alpha-methyl-4-tetrazolylphenylglycine (MTPG) or the adenosine receptor antagonist 8-phenyltheophylline. Furthermore, a strong s ynergistic effect was observed when the striatal membranes were exposed to both CGS 21680 and 1S-3R-ACPD. In agreement with the biochemical results, i n unilaterally 6-OH-dopamine lesioned rats 1S-3R-ACPD counteracted the turn ing behaviour induced by the D-2 receptor agonist quinpirole, but not by th e D-1 receptor agonist SKF 38393, and it synergistically potentiated the an tagonistic effect of CGS 21680 on quinpirole-induced turning behaviour. (C) 1999 Elsevier Science Ltd. All rights reserved.