LOCALIZATION OF DOPAMINE D-3 RECEPTORS TO MESOLIMBIC AND D-2 RECEPTORS TO MESOSTRIATAL REGIONS OF HUMAN FOREBRAIN

We characterized the binding of [I-125]epidepride to dopamine D-2-like and D-3-like receptors in tissue sections of human striatum. The competition for binding of [I-125]epidepride by domperidone, quinpirole, and 7-hydroxy-N,N-di(1-propyl)-2-aminotetralin (7-OH-DPAT) was best fit by assuming one site in the caudate but two sites in nucleus accumbens. Guanosine 5'-[beta,gamma-imido]triphosphate showed a large modulatory influence in agonist inhibition of [I-125]epidepride binding in caudate but not in nucleus accumbens. The binding of [I-125]epidepride in the presence of 7-OH-DPAT (1000-fold selective for D-3-like versus D-2-like sites) and domperidone (20-fold selective for D-2-like versus D-3-like sites) was used to quantify the numbers of D-2-like and D-3-like receptors in areas of human brain. The distribution of D-2-like and D-3-like receptors was largely nonoverlapping. Binding of [I-125]epidepride to D-3-like receptors was negligible in the dorsal striatum but was concentrated in islands of dense binding in the nucleus accumbens and ventral putamen that aligned with acetylcho linesterase-poor striosomes. Binding to D-3-like receptors was also enriched in the internal globus pallidus, ventral pallidum, septum, islands of Calleja, nucleus basalis, amygdalostriatal transition nucleus of the amygdala, central nucleus of the amygdala, and ventral tegmental area. Binding of [I-125]epidepride to D-2 but not D-3 receptors was detected in cortex and hippocampus.