GABA-dopamine receptor-receptor interactions in neostriatal membranes of the rat

Recent evidence has shown in membrane preparations that the binding of one ligand to its receptor is able to modify the binding parameters of a second receptor (receptor-receptor interactions), allowing the modulation of incoming signals onto a neuron. To further understand the gamma-aminobutyric acid (GABA)-dopamine (DA) interactions in the neostriatum we have carried out experiments to explore whether an activation of the GABA(A) receptor could affect the binding characteristics of the D-2 DA receptor in membrane preparations of the rat neostriatum. The results show that GABA (30-100 nM) significantly increases the dissociation constant of the high affinity (K-H) D-2 DA binding site (labelled with the selective D-2 DA receptor antagonist [H-3]raclopride and that such an effect is fully counteracted by the GABA(A) receptor antagonist bicuculline (1 mu M). It is suggested that such putative GABA(A)/D-2 receptor-receptor interactions may take place in the somato-dendritic membrane of the striato-pallidal GABA neurons and that it may modulate the inhibitory effects of DA on these neurons, mediated via D-2 receptors.