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Dopamine D 2 and D 3 receptors in the rat striatum and nucleus accumbens: Use of 7‐OH‐DPAT and [ 125 I]‐Iodosulpride
Author(s) -
Booze Rosemarie M.,
Wallace David R.
Publication year - 1995
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890190102
Subject(s) - nucleus accumbens , dopamine receptor d3 , dopamine receptor d2 , receptor , striatum , dopamine receptor , dopamine , ventral striatum , biology , chemistry , medicine , ventral pallidum , basal ganglia , endocrinology , biochemistry , central nervous system , globus pallidus
A novel dopamine receptor mRNA transcript has been identified and classified as the D 3 receptor subtype. We have examined the binding of the D2/D3‐selective compound [ 125 I]‐Iodosulpride using unlabeled D 3 ‐selective 7‐OH‐DPAT to determine the distribution of D2 and D3 dopamine receptor subtypes in the rat basal forebrain. Use of [ 125 I]‐labeled ligands has significant advantages over [ 3 H]‐labeled compounds for autoradiographic studies, especially for evaluating small brain areas containing low receptor densities. [ 125 I]‐Iodosulpride identified two sites with high affinity (<1 nM) in the presence of (‐)sulpiride (μM; 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. [ 125 I]‐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 [ 125 I]‐Iodosulpride to label the dopamine receptor subtypes are high specific activity, affinity, and lack of quenching in autoradiographic analyses. Moreover, masking D3 receptors with 7‐OH‐DPAT permitted indirect determination of D 3 receptor density and localization using the [ 125 I]‐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. © 1995 Wiley‐Liss, Inc.