title: Attenuation of the effect of progesterone and 4'-chlordiazepam on stress-induced immune responses by bicuculline.
abstract: The present study investigates the effect of progesterone, a pregnane precursor of neurosteroids, and 4'-chlordiazepam (4'-CD), a specific ligand for mitochondrial diazepam binding inhibitor receptor (MDR) involved in neurosteroidogenesis, on restraint stress (RS)-induced modulation of humoral and cell-mediated immune responses. RS produced a significant reduction in anti-sheep red blood cells (SRBC) antibody titre, a measure of humoral immune response, and % leucocyte migration inhibition (LMI) and foot-pad thickness test, measures of cell-mediated immune responses. These effects of RS on immune responses were effectively blocked by pretreating the animals with progesterone (10 mg/kg, sc) or 4'-CD (0.5 mg/kg, sc) administered just before subjecting the animal to RS. The effect of both progesterone and 4'-CD on RS-induced immune modulation was significantly attenuated by bicuculline (2 mg/kg, ip) but not by flumazenil (10 mg/kg, ip). Unlike its effect on RS-induced immune responsiveness, progesterone (5, 10 mg/kg, sc) when administered to non-stressed animals produced a significant suppression of both humoral and cell-mediated immune responses which was not reversed by bicuculline. However, 4'-CD failed to modulate immune response in naive non-stressed animals. These results suggest that progesterone and 4'-CD affect stress-induced immune responses by modulating GABA-ergic mechanism. However, GABA-A receptor system does not appear to be involved in progesterone-induced immunosuppression in nonstressed animals.
authors.affiliation: Department of Pharmacology, University College of Medical Sciences & GTB Hospital, Delhi 110 095.
authors.forename: P K
authors.initials: PK
authors.lastname: Mediratta
authors.forename: J
authors.initials: J
authors.lastname: Bhatia
authors.forename: S
authors.initials: S
authors.lastname: Tewary
authors.forename: V
authors.initials: V
authors.lastname: Katyal
authors.forename: P
authors.initials: P
authors.lastname: Mahajan
authors.forename: K K
authors.initials: KK
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001640:Bicuculline / Q000494:pharmacology*; D002464:Cell Migration Inhibition; D003975:Diazepam / Q000031:analogs & derivatives / Q000494:pharmacology*; D026261:Diazepam Binding Inhibitor / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D018756:GABA Antagonists / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects*; D008297:Male; D051379:Mice; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000276:immunology*
chemical_list: C488690:4'-chlordiazepam; D026261:Diazepam Binding Inhibitor; D018756:GABA Antagonists; D006993:Hypnotics and Sedatives; D011374:Progesterone; D003975:Diazepam; D001640:Bicuculline