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Identification of D 3 and σ Receptors in the Rat Striatum and Nucleus Accumbens Using (±)‐7‐Hydroxy‐ N , N ‐Di‐ n ‐[ 3 H]Propyl‐2‐Aminotetralin and Carbetapentane
Author(s) -
Wallace David R.,
Booze Rosemarie M.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64020700.x
Subject(s) - nucleus accumbens , chemistry , dopamine receptor d3 , receptor , striatum , radioligand , spiperone , dopamine receptor , stereochemistry , dopamine , microbiology and biotechnology , biology , biochemistry , endocrinology
Cross‐reactions between dopamine D 3 and σ receptor ligands were investigated using (±)‐7‐hydroxy‐ N,N ‐di‐ n ‐[ 3 H]propyl‐2‐aminotetralin [(±)‐7‐OH‐[ 3 H]DPAT], a putative D 3 ‐selective radioligand, in conjunction with the unlabeled σ ligands 1,3‐di(2‐tolyl)guanidine (DTG), carbetapentane, and R (−)‐ N ‐(3‐phenyl‐1‐propyl)‐1‐phenyl‐2‐aminopropane [ R (−)‐PPAP]. In transfected CCL1.3 mouse fibroblasts expressing the human D 3 receptor, neither DTG nor carbetapentane (0.1 µ M ) displaced (±)‐7‐OH‐[ 3 H]DPAT binding. R (−)‐PPAP (0.1 µ M ) displaced 39.6 ± 1.0% of total (±)‐7‐OH‐[ 3 H]DPAT binding. In striatal and nucleus accumbens homogenates, (±)‐7‐OH‐[ 3 H]DPAT labeled a single site (15–20 fmol/mg of protein) with high (1 n M ) affinity. Competition analysis with carbetapentane defined both high‐ and low‐affinity sites in striatal (35 and 65%, respectively) and nucleus accumbens (59 and 41%, respectively) tissue, yet R (−)‐PPAP identified two sites in equal proportion. Carbetapentane and R (−)‐PPAP (0.1 µ M ) displaced ∼20–50% of total (±)‐7‐OH‐[ 3 H]DPAT binding in striatum, nucleus accumbens, and olfactory tubercle in autoradiographic studies, with the nucleus accumbens shell subregion exhibiting the greatest displacement. To determine directly (+)‐7‐OH‐[ 3 H]DPAT binding to σ receptors, saturation analysis was performed in the cerebellum while masking D 3 receptors with 1 µ M dopamine. Under these conditions (+)‐7‐OH‐[ 3 H]DPAT labeled σ receptors with an affinity of 24 n M . These results suggest that (a) (±)‐7‐OH‐[ 3 H]DPAT binds D 3 receptors with high affinity in rat brain and (b) a significant proportion of (±)‐7‐OH‐[ 3 H]DPAT binding consists of σ 1 sites and the percentages of these sites differ among the subregions of the striatum and nucleus accumbens.