AUTORADIOGRAPHIC LOCALIZATION OF [H-3] QUINPIROLE BINDING TO DOPAMINE-D2 AND DOPAMINE-D3 RECEPTORS IN RAT-BRAIN

A radiolabelled form of the dopamine agonist, quinpirole (LY17155), has been evaluated as a ligand for dopamine receptors in the rat brain. Quinpirole has been reported to be a selective D2 dopamine agonist; however, a recent report has indicated that it may have high affinity for a novel dopamine binding site which has been termed D3. In rat brain sections, [H-3]quinpirole binding exhibited a distribution similar to that described for dopamine D2 receptors using either agonist or antagonist labelling. High densities of binding could be found in caudate-putamen, nucleus accumbens, olfactory tubercle and islands of Calleja. When the labelling was done in the presence of 10-mu-M guanylyl-5'-imidodiphosphate to convert the dopamine D2 receptor to a 'low affinity agonist conformation', binding was inhibited in most brain regions with the notable exception of the islands of Calleja which retained most of the [H-3]quinpirole binding. The guanine nucleotide insensitivity of this binding and distribution of this site indicates that [H-3]quinpirole is binding to dopamine D3 receptors in this region of the brain. Therefore, these results indicate that [H-3]quinpirole labels a high affinity agonist conformation of dopamine D2 receptors as well as dopamine D3 receptors in rat brain. In addition, this study provides the first detection the dopamine D3 receptor protein in the brain.