Involvement of sigma (sigma1) receptors in modulating the anti-depressant effect of neurosteroids (dehydroepiandrosterone or pregnenolone) in mouse tail-suspension test.

The present study investigated the effects of neurosteroids dehydroepiandrosterone sulfate (DHEAS) or pregnenolone sulfate (PS) on the tail-suspension test (TST) of depression in mice, and also the possible involvement of sigma (sigma) receptors. Immobility time in the TST was measured for a total period of 6 min. DHEAS (10 and 40 mg/kg, s.c.) or PS (40 mg/kg, s.c.) significantly reduced the immobility period without accompanying changes in the locomotor activity in mice. The effect on behavioural despair by DHEAS (10 and 40 mg/kg, s.c.) and PS (40 mg/kg, s.c.) was blocked by BD 1047 (1 mg/kg, s.c.), a novel sigma1-receptor antagonist, progesterone (10 mg/kg, s.c.), a sigma-receptor antagonistic neurosteroid or rimcazole (5 mg/kg, s.c.), another sigma1-receptor antagonistic property, respectively. The treatments and their combination did not alter the motor activity in mice. These data suggested a role for the central sigma receptors particularly sigma-1 (sigma1) receptors in the anti-depressant-like effects of neurosteroids.