Modulation of the in vivo antibody response by a benzodiazepine inverse agonist (DMCM) administered centrally or peripherally.

ABSTRACT

Exposure to stressors can result in changes in immune function. Although there is increasing information concerning the peripheral hormonal and neural mediators of stress-induced changes in immune function, there is little information concerning the central nervous system mechanisms that lead to the peripheral changes. The following experiments examined the possible involvement of the benzodiazepine-GABAA-chloride complex in modulation of the in vivo antibody response. Rats were given either peripheral or intracerebroventricular injections of methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), a drug that has been shown to act at the benzodiazepine-GABAA complex and produces a behavioral state similar to anxiety. Rats were then immunized with keyhole limpet hemocyanin (KLH) and serum levels of KLH-specific antibody were measured for 2 weeks after immunization. Both peripheral and central administration of DMCM modulated the in vivo antibody response. The dose-response relationship of DMCM and changes in antibody levels was nonmonotonic, with high doses resulting in an increase in serum antibody levels and moderate doses resulting in a decrease in serum antibody levels. A possible role of the benzodiazepine-GABAA system in stress-induced immunomodulation is discussed.