Identification of D3 and σ Receptors in the Rat Striatum and Nucleus Accumbens Using (±)‐7‐Hydroxy‐N,N‐Di‐n‐[3H]Propyl‐2‐Aminotetralin and Carbetapentane

David R. Wallace, Rosemarie M. Booze

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39 Citations (Scopus)

Abstract

Abstract: Cross‐reactions between dopamine D3 and σ receptor ligands were investigated using (±)‐7‐hydroxy‐N,N‐di‐n‐[3H]propyl‐2‐aminotetralin [(±)‐7‐OH‐[3H]DPAT], a putative D3‐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 D3 receptor, neither DTG nor carbetapentane (0.1 µM) displaced (±)‐7‐OH‐[3H]DPAT binding. R(−)‐PPAP (0.1 µM) displaced 39.6 ± 1.0% of total (±)‐7‐OH‐[3H]DPAT binding. In striatal and nucleus accumbens homogenates, (±)‐7‐OH‐[3H]DPAT labeled a single site (15–20 fmol/mg of protein) with high (1 nM) 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 µM) displaced ∼20–50% of total (±)‐7‐OH‐[3H]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‐[3H]DPAT binding to σ receptors, saturation analysis was performed in the cerebellum while masking D3 receptors with 1 µM dopamine. Under these conditions (+)‐7‐OH‐[3H]DPAT labeled σ receptors with an affinity of 24 nM. These results suggest that (a) (±)‐7‐OH‐[3H]DPAT binds D3 receptors with high affinity in rat brain and (b) a significant proportion of (±)‐7‐OH‐[3H]DPAT binding consists of σ1 sites and the percentages of these sites differ among the subregions of the striatum and nucleus accumbens.

Original languageEnglish
Pages (from-to)700-710
Number of pages11
JournalJournal of Neurochemistry
Volume64
Issue number2
DOIs
StatePublished - 1 Jan 1995

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Nucleus Accumbens
Rats
Corpus Striatum
Dopamine D3 Receptors
Ligands
Guanidine
Fibroblasts
Dopamine
Brain
Cerebellum
Tissue
carbetapentane
N-(3-phenyl-n-propyl)-1-phenyl-2-aminopropane
Proteins

Keywords

  • Autoradiography
  • Dopaminergic system
  • Nucleus accumbens
  • Striatum

Cite this

@article{de0fe8cb44f946a48528720ff58d19fd,
title = "Identification of D3 and σ Receptors in the Rat Striatum and Nucleus Accumbens Using (±)‐7‐Hydroxy‐N,N‐Di‐n‐[3H]Propyl‐2‐Aminotetralin and Carbetapentane",
abstract = "Abstract: Cross‐reactions between dopamine D3 and σ receptor ligands were investigated using (±)‐7‐hydroxy‐N,N‐di‐n‐[3H]propyl‐2‐aminotetralin [(±)‐7‐OH‐[3H]DPAT], a putative D3‐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 D3 receptor, neither DTG nor carbetapentane (0.1 µM) displaced (±)‐7‐OH‐[3H]DPAT binding. R(−)‐PPAP (0.1 µM) displaced 39.6 ± 1.0{\%} of total (±)‐7‐OH‐[3H]DPAT binding. In striatal and nucleus accumbens homogenates, (±)‐7‐OH‐[3H]DPAT labeled a single site (15–20 fmol/mg of protein) with high (1 nM) 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 µM) displaced ∼20–50{\%} of total (±)‐7‐OH‐[3H]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‐[3H]DPAT binding to σ receptors, saturation analysis was performed in the cerebellum while masking D3 receptors with 1 µM dopamine. Under these conditions (+)‐7‐OH‐[3H]DPAT labeled σ receptors with an affinity of 24 nM. These results suggest that (a) (±)‐7‐OH‐[3H]DPAT binds D3 receptors with high affinity in rat brain and (b) a significant proportion of (±)‐7‐OH‐[3H]DPAT binding consists of σ1 sites and the percentages of these sites differ among the subregions of the striatum and nucleus accumbens.",
keywords = "Autoradiography, Dopaminergic system, Nucleus accumbens, Striatum",
author = "Wallace, {David R.} and Booze, {Rosemarie M.}",
year = "1995",
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doi = "10.1046/j.1471-4159.1995.64020700.x",
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volume = "64",
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journal = "Journal of Neurochemistry",
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TY - JOUR

T1 - Identification of D3 and σ Receptors in the Rat Striatum and Nucleus Accumbens Using (±)‐7‐Hydroxy‐N,N‐Di‐n‐[3H]Propyl‐2‐Aminotetralin and Carbetapentane

AU - Wallace, David R.

AU - Booze, Rosemarie M.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - Abstract: Cross‐reactions between dopamine D3 and σ receptor ligands were investigated using (±)‐7‐hydroxy‐N,N‐di‐n‐[3H]propyl‐2‐aminotetralin [(±)‐7‐OH‐[3H]DPAT], a putative D3‐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 D3 receptor, neither DTG nor carbetapentane (0.1 µM) displaced (±)‐7‐OH‐[3H]DPAT binding. R(−)‐PPAP (0.1 µM) displaced 39.6 ± 1.0% of total (±)‐7‐OH‐[3H]DPAT binding. In striatal and nucleus accumbens homogenates, (±)‐7‐OH‐[3H]DPAT labeled a single site (15–20 fmol/mg of protein) with high (1 nM) 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 µM) displaced ∼20–50% of total (±)‐7‐OH‐[3H]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‐[3H]DPAT binding to σ receptors, saturation analysis was performed in the cerebellum while masking D3 receptors with 1 µM dopamine. Under these conditions (+)‐7‐OH‐[3H]DPAT labeled σ receptors with an affinity of 24 nM. These results suggest that (a) (±)‐7‐OH‐[3H]DPAT binds D3 receptors with high affinity in rat brain and (b) a significant proportion of (±)‐7‐OH‐[3H]DPAT binding consists of σ1 sites and the percentages of these sites differ among the subregions of the striatum and nucleus accumbens.

AB - Abstract: Cross‐reactions between dopamine D3 and σ receptor ligands were investigated using (±)‐7‐hydroxy‐N,N‐di‐n‐[3H]propyl‐2‐aminotetralin [(±)‐7‐OH‐[3H]DPAT], a putative D3‐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 D3 receptor, neither DTG nor carbetapentane (0.1 µM) displaced (±)‐7‐OH‐[3H]DPAT binding. R(−)‐PPAP (0.1 µM) displaced 39.6 ± 1.0% of total (±)‐7‐OH‐[3H]DPAT binding. In striatal and nucleus accumbens homogenates, (±)‐7‐OH‐[3H]DPAT labeled a single site (15–20 fmol/mg of protein) with high (1 nM) 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 µM) displaced ∼20–50% of total (±)‐7‐OH‐[3H]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‐[3H]DPAT binding to σ receptors, saturation analysis was performed in the cerebellum while masking D3 receptors with 1 µM dopamine. Under these conditions (+)‐7‐OH‐[3H]DPAT labeled σ receptors with an affinity of 24 nM. These results suggest that (a) (±)‐7‐OH‐[3H]DPAT binds D3 receptors with high affinity in rat brain and (b) a significant proportion of (±)‐7‐OH‐[3H]DPAT binding consists of σ1 sites and the percentages of these sites differ among the subregions of the striatum and nucleus accumbens.

KW - Autoradiography

KW - Dopaminergic system

KW - Nucleus accumbens

KW - Striatum

UR - http://www.scopus.com/inward/record.url?scp=0028980498&partnerID=8YFLogxK

U2 - 10.1046/j.1471-4159.1995.64020700.x

DO - 10.1046/j.1471-4159.1995.64020700.x

M3 - Article

C2 - 7830063

AN - SCOPUS:0028980498

VL - 64

SP - 700

EP - 710

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 2

ER -