Sigma1 and dopamine D2 receptor occupancy in the mouse brain after a single administration of haloperidol and two dopamine D2-like receptor ligands

We investigated sigma, and dopamine D-2 receptor occupancy in mouse brain after a single injection of haloperidol, nemonapride, or spiperone using [C-11]SA4503 and [C-11]raclopride, respectively. Co-injection of the three compounds significantly blocked the uptake of each radioligand. Six hours later, only haloperidol blocked [C-11]SA4503 uptake, while all three reduced [C-11]raclopride uptake. Sigma(1) receptor occupancy by haloperidol was reduced to 19% at day 2 when D-2 receptor occupancy disappeared. [C-11]SA4503 would be applicable to the investigation of sigma, receptor occupancy of antispychotic drugs using PET. (C) 2003 Elsevier Inc. All rights reserved.