SKF-10,047 reverses stress-induced motor suppression: interaction with dopaminergic system

Mice exhibited a marked suppression of motility (conditioned suppression) when placed in the same environment in which they had previously received an electric footshock. This stress-induced motor suppression was dose dependently attenuated by (±)-SKF-10,047, a σ receptor agonist, but not by its (-)-optical isomer ((-)-SKF-10,047) and the σ receptor ligands (+)-pentazocine and 1,3-di(2-tolyl)guanidine. This effect of (±)-SKf-10,047 was antagonized by BMY-14802, a σ receptor antagonist, and by pimozide, a dopamine receptor antagonist. When dopaminergic neurons were destroyed by pretreatment with 6-hydroxydopamine, the effect of (±)-SKF-10,047 on the stress response was also attenuated. Furthermore, (±)-SKF-10,047 dose dependently reversed the decrease in striatal dopamine turnover in the conditioned suppression group. These results suggest that stress-induced motor suppression is restored by (±)-SKF-10,047 acting through σ receptors, which are closely linked to the dopaminergic neuronal system.