MODULATION OF THE IN-VIVO ANTIBODY-RESPONSE BY A BENZODIAZEPINE INVERSE AGONIST (DMCM) ADMINISTERED CENTRALLY OR PERIPHERALLY

Exposure to stressors can result in changes in immune function. Althou gh there is increasing information concerning the peripheral hormonal and neural mediators of stress-induced changes in immune function, the re is little information concerning the central nervous system mechani sms that lead to the peripheral changes. The following experiments exa mined the possible involvement of the benzodiazepine-GABA(A)-chloride complex in modulation of the in vivo antibody response. Rats were give n either peripheral or intracerebroventricular injections of 6,7-dimet hoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), a drug that has been shown to act at the benzodiazepine-GABA(A), complex and produces a be havioral state similar to anxiety. Rats were then immunized with keyho le limpet hemocyanin (KLH) and serum levels of KLH-specific antibody w ere measured for 2 weeks after immunization. Both peripheral and centr al 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 antib ody levels and moderate doses resulting in a decease in serum antibody levels. A possible role of the benzodiazepine-GABA(A), system in stre ss-induced immunomodulation is discussed.