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.
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Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
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D000818:Animals; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D005029:Ethylenediamines / Q000494:pharmacology; D007103:Immobilization / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011284:Pregnenolone / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology*; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D013623:Tail / Q000502:physiology
D005029:Ethylenediamines; D017480:Receptors, sigma; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin; D003687:Dehydroepiandrosterone; D011374:Progesterone; D011284:Pregnenolone