Central GABAA and GABAB receptor modulation of basal and stress-induced plasma interleukin-6 levels in mice.

To investigate the modulatory roles of central gamma-aminobutyric acid (GABA)A and GABAB 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 GABAA receptor agonist, and baclofen (5-20 ng), a GABAB 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 GABAA receptor antagonist, and 2-hydroxysaclofen (1-10 microgram), a GABAB receptor 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 microg i.c.v.)-induced increase in the basal plasma IL-6 levels. These data suggest that central GABAA and GABAB receptors are involved in the suppressive modulation of basal and restraint stress-induced plasma IL-6 levels in mice.