CENTRAL GABA(A) AND GABA(B) RECEPTOR MODULATION OF BASAL AND STRESS-INDUCED PLASMA INTERLEUKIN-6 LEVELS IN MICE

To investigate the modulatory roles of central gamma-aminobutyric acid (GABA), and GABA, receptors in the regulation of basal and stress-ind uced 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, receptor agonist, and baclofen (5-20 ng), a GABA, recepto r agonist, injected i.c.v. did not affect the basal levels of plasma I L-6. In the restraint-stressed animals, muscimol and baclofen inhibite d the stress-induced plasma IL-6 levels from the dose of 50 and 15 ng, respectively. Carboxyl)-3-amino-6-(4-methoxyphenyl)-pyridazinium brom ide (SR-95,531; 0.3-10 ng), a GABA(A) receptor antagonist, and 2-hydro xysaclofen (1-10 mu g), a GABA, receptor antagonist, injected i.c.v. i ncreased both the basal and the restraint stress-induced plasma IL-6 l evels. 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 n ot 2-hydroxysaclofen (10 mu g i.c.v.)-induced increase in the basal pl asma IL-6 levels. These data suggest that central GABA, and GABA, rece ptors are involved in the suppressive modulation of basal and restrain t stress-induced plasma IL-6 levels in mice.