Antidepressant-like effect of combined treatment with selective sigma receptor agonists and a 5-HT1A receptor agonist in the forced swimming test in rats.

The interaction between the selective sigma (sigma) receptor agonists and 8-OH-DPAT, a serotonin (5-HT)(1A) receptor agonist, was examined in the forced swimming test in rats. The results indicate that joint administration of DTG (5 mg/kg) or SA4503 (3 mg/kg), the selective sigma(1)/sigma(2)- or sigma(1)-receptor agonists, respectively, and 8-OH-DPAT (0.1 or 0.3 mg/kg) induces an antidepressant-like effect. The doses of sigma agonists and 8-OH-DPAT used in the study were inactive per se in this model. The effect of DTG and 8-OH-DPAT co-administration was partly counteracted by WAY 100635 (0.1 mg/kg) as well as by BD 1047 (3 mg/kg), a 5-HT(1A) and sigma(1) receptor antagonists, respectively, suggesting the involvement of both receptor types in the anti-immobility effect in rats.