ROLE OF (-SKF-10,047-SENSITIVE SUBPOPULATION OF SIGMA(1) RECEPTORS INAMELIORATION OF CONDITIONED FEAR STRESS IN RATS - ASSOCIATION WITH MESOLIMBIC DOPAMINERGIC SYSTEMS())

Rats exhibited a marked suppression of motility when they were re-plac ed in the same environment as that in which they had previously receiv ed an electric footshock. We examined the behavioral and neurochemical effects of (+)-N-allylhormetazocine hydrochloride ((+)-SKF-10,047) an d (+)-pentazocine, putative sigma(1) receptor ligands, on this psychol ogical-stress-induced motor suppression, defined as a conditioned fear stress. (+)-SKF-10,047 (3 and 6 mg/kg) dose-dependently attenuated th e conditioned fear stress, whereas (+)-pentazocine failed to do so eve n at a higher dose (32 mg/kg). In rats showing the conditioned fear st ress, dopamine turnover (i.e., the ratio of dopamine metabolites/dopam ine contents) was decreased in the nucleus accumbens and was increased in the medial prefrontal cortex, but remained unchanged in the striat um. (+)-SKF-10,047 (3 and 6 mg/kg) dose-dependently reversed the decre ased dopamine turnover in the nucleus accumbens without changing the i ncreased dopamine turnover in the medial prefrontal cortex. (+)-Pentaz ocine (32 mg/kg) did not affect the stress-induced changes in dopamine turnover in these brain regions. Thus, the decreased dopamine turnove r in the nucleus accumbens appears to be involved in the conditioned f ear stress. These results suggest that (+)-SKF-10,047 ameliorates the conditioned fear stress by reversing the psychological stress-induced dysfunction in the mesolimbic dopaminergic systems, and that the (+)-S KF-10,047-sensitive sub-population of sigma(1) receptors may play an i mportant role in this stress response.