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

Publisher Website
Google Scholar
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.

This publication has 0 references indexed in Scilit: