[11C]Raclopride binding was reduced in vivo by sigma1 receptor ligand SA4503 in the mouse brain, while [11C]SA4503 binding was not by raclopride

[C-11]Raclopride is widely used as a representative dopamine D-2-like receptor ligand in positron emission tomography (PET) studies, and [C-11]1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride ([C-11]SA4503) is a recently developed selective Ligand for mapping sigma(1) receptors in the brain. The striatal uptake of [C-11]raclopride in mice was reduced by co-injection of an excess amount of SA4503, in spite of the fact that raclopride had no effect on the brain uptake of [C-11]SA4503 as shown in a previous study. The blocking effect of SA4503 on the striatal uptake of [C-11]raclopride was dose-dependent, but disappeared by 1 h or 6 h after intraperitoneal injection of SA4503. The brain uptake of [C-11]SA4503 was not affected by a dopamine transporter inhibitor GBR 12909, nor was [C-11]beta -CIT-FP inhibited by SA4503. The IC50 values of raclopride for sigma, and sigma(2) receptor subtypes measured in vitro were 11800 nM and 4950 nM, respectively, suggesting that the affinity was too low for [C-11]raclopride to bind in vivo to sigma receptors. On the other hand, the IC50 value of SA4503 for dopamine D-2 receptors was 470 nM, that is approximate 1/25 of the affinity of raclopride for the dopamine D-2 receptors. Therefore, possible explanations for the partial blocking effects of SA4503 on the striatal uptake of [C-11]raclopride are: (1) an excess amount of SA4503 may reduce the [C-11]raclopride uptake due to its low affinity for dopamine D-2 receptors, or (2) SA4503 may enhance endogenous dopamine release, which results in the competitive inhibition of the [C-11]raclopride uptake. These findings support that both [C-11]raclopride and [C-11]SA4503 are selective in vivo ligands for dopamine D-2-like receptors and sigma, receptors, respectively, in spite of the partial blocking effect of SA4503 on the striatal uptake of [C-11]raclopride. (C) 2001 Elsevier Science Inc. All rights reserved.