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Involvement of sigma (1) receptors in modulating the anti-depressant effect of neurosteroids (dehydroepiandrosterone or pregnenolone) in mouse tail-suspension test

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India

SK Kulkarni

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India, skpu{at}yahoo.com

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 () 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 ₁-receptor antagonist, progesterone (10 mg/kg, s.c.), a -receptor antagonistic neurosteroid or rimcazole (5 mg/kg, s.c.), another ₁-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 receptors particularly sigma-1 (₁) receptors in the anti-depressant-like effects of neurosteroids.

Key Words: neurosteroids • depression • tail-suspension test • sigma receptors

This version was published on August 1, 2008

Journal of Psychopharmacology, Vol. 22, No. 6, 691-696 (2008)
DOI: 10.1177/0269881107082771


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