1. Attenuation of the effect of progesterone and 4'-chlordiazepam on stress-induced immune responses by bicuculline.
- Author
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Mediratta PK, Bhatia J, Tewary S, Katyal V, Mahajan P, and Sharma KK
- Subjects
- Animals, Cell Migration Inhibition, Diazepam analogs & derivatives, Diazepam Binding Inhibitor pharmacology, Dose-Response Relationship, Drug, Edema chemically induced, Edema pathology, Male, Mice, Rats, Rats, Wistar, Restraint, Physical, Antibody Formation drug effects, Bicuculline pharmacology, Diazepam pharmacology, GABA Antagonists pharmacology, Hypnotics and Sedatives pharmacology, Immunity, Cellular drug effects, Progesterone pharmacology, Stress, Psychological immunology
- 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.
- Published
- 2003