SKF-10,047 REVERSES STRESS-INDUCED MOTOR SUPPRESSION INTERACTION WITHDOPAMINERGIC SYSTEM

Mice exhibited a marked suppression of motility (conditioned suppressi on) when placed in the same environment in which they had previously r eceived an electric footshock. This stress-induced motor suppression w as dose dependently attenuated by (+/-)-SKF-10,047, a sigma receptor a gonist, but not by its (-)-optical isomer ((-)-SKF-10,047) and the sig ma receptor ligands (+)-pentazocine and 1,3-di-(2-tolyl)guanidine. Thi s effect of (+/-)-SKF-10,047 was antagonized by BMY-14802, a sigma rec eptor antagonist, and by pimozide, a dopamine receptor antagonist. Whe n dopaminergic neurons were destroyed by pretreatment with 6-hydroxydo pamine, the effect of (+/-)-SKF-10,047 on the stress response was also attenuated. Furthermore, (+/-)-SKF-10,047 dose dependently reversed t he decrease in striatal dopamine turnover in the conditioned suppressi on group. These results suggest that stress-induced motor suppression is restored by (+/-)-SKF-10,047 acting through sigma receptors, which are closely linked to the dopaminergic neuronal system.