SIGMA (SIGMA(1)) RECEPTOR-MEDIATED ANTIDEPRESSANT-LIKE EFFECTS OF NEUROSTEROIDS IN THE PORSOLT FORCED SWIM TEST

THIS study examined the effects of neurosteroids dehydroepiandrosteron e sulfate (DHEAS) and pregnenolone sulfate (PS) and progesterone on th e Porsolt forced swim test of depression in mice, and investigated the possible involvement of a receptors. The immobility time in the mouse forced swimming test was significantly reduced by DHEAS (5 and 20 mg/ kg, s.c.) and PS (5 mg/kg) without accompanying changes in the ambulat ory or open-field activity. Pretreatment with DHEAS (10 mg/kg) or PS ( 10 and 20mg/kg), however, failed to modify the immobility. The relief of behavioral despair in the immobility test by DHEAS (5 and 20mg/kg) was dose-dependently blocked by preadministration of NE-100 (N,N-dipro pyl-2-[4-methoxy-3- (2-phenylethoxy)phenyl-ethylamine monohydrochlorid e; 0.5 and 1 mg/kg), a putative al receptor antagonist, or progesteron e (10mg/kg), a a receptor antagonistic neurosteroid. On the other hand , PS (5 mg/kg)-induced decrease in the immobility was significantly bl ocked by NE-100 (0.5 mg/kg), but not by progesterone (10 mg/kg). Neith er NE-100 nor progesterone influenced the immobility alone. These data suggest a role for central a receptor in the antidepressant-like effe cts of neurosteroids, and reinforced their potential therapeutic use i n depression. NeuroReport 9: 3069-3073 (C) 1998 Lippincott Williams & Wilkins.