Abstract

To investigate the modulatory roles of central γ-aminobutyric acid (GABA)_A and GABA_B receptors in the regulation of basal and stress-induced plasma interleukin-6 (IL-6) levels, we examined the effects of i.c.v. injection of GABA receptor agonists and antagonists on basal and restraint stress-induced plasma IL-6 levels in mice. Muscimol (20–200 ng), a GABA_A receptor agonist, and baclofen (5–20 ng), a GABA_B receptor agonist, injected i.c.v. did not affect the basal levels of plasma IL-6. In the restraint-stressed animals, muscimol and baclofen inhibited the stress-induced plasma IL-6 levels from the dose of 50 and 15 ng, respectively. 2-(3-Carboxyl)-3-amino-6-(4-methoxyphenyl)-pyridazinium bromide (SR-95,531; 0.3–10 ng), a GABA_A receptor antagonist, and 2-hydroxysaclofen (1–10 μg), a GABA_Breceptor antagonist, injected i.c.v. increased both the basal and the restraint stress-induced plasma IL-6 levels. The i.p. pretreatment of animals with 6-hydroxydopamine (100 mg/kg) for 3 days significantly inhibited SR-95,531 (3 ng i.c.v.)- but not 2-hydroxysaclofen (10 μg i.c.v.)-induced increase in the basal plasma IL-6 levels. These data suggest that central GABA_A and GABA_B receptors are involved in the suppressive modulation of basal and restraint stress-induced plasma IL-6 levels in mice.