DOPAMINE D-2 AND D-3 RECEPTORS IN THE RAT STRIATUM AND NUCLEUS-ACCUMBENS - USE OF 7-OH-DPAT AND [I-125] IODOSULPRIDE

A novel dopamine receptor mRNA transcript has been identified and classified as the D-3 receptor subtype. We have examined the binding of the D-2/D-3-selective compound [I-125]-Iodosulpride using unlabeled D-3-selective 7-OH-DPAT to determine the distribution of D-2 and D-3 dopamine receptor subtypes in the rat basal forebrain. Use of[I-125]-labeled ligands has significant advantages over [H-3]-labeled compounds for autoradiographic studies, especially for evaluating small brain areas containing low receptor densities. [I-125]-Iodosulpride identified two sites with high affinity (< 1 nM) in the presence of (-)sulpiride (1 mu M; D-2+3) or 7-OH-DPAT (10 nM; D-3), with a greater density of D-2 receptors (twofold) compared to D-3 receptors in the striatum. The density of D-2 and D-3 receptor subtypes displayed a 1:1 ratio in the nucleus accumbens. [I-125]- Iodosulpride with 7-OH-DPAT displayed D-2 sites, predominately in the striatum. Digital subtraction autoradiography showed the highest levels of D-3 binding in the islands of Calleja as well as in the core and shell regions of the nucleus accumbens. In sum, the advantages in using [I-125]-Iodosulpride to label the dopamine receptor subtypes are high specific activity, affinity, and lack of quenching in autoradiographic analyses. Moreover, masking D-3 receptors with 7-OH-DPAT permitted indirect determination of D-3 receptor density and localization using the [I-125]-labeled ligand, without the potential confound of 7-OH-DPAT binding to sigma receptors. The colocalization of the D-2 dopamine receptors with D-3 receptors suggests that unique interactions may exist between the receptor subtypes in the rat basal forebrain region. (C) 1995 Wiley-Liss, Inc.