Involvement of supraspinal GABA-ergic systems in clonidine-induced antinociception in the tail-pinch test in mice

Abstract

We investigated the involvement of supraspinal GABAergic systems in the antinociceptive effect of clonidine using the tail-pinch test in mice. Muscimol (31.2–250 ng/mouse, i.c.v.) and R(+)-baclofen (10–100 ng/mouse, i.c.v.), selective agonists for the GABA a and GABA b receptors, respectively, significantly attenuated the antinociceptive effect of subcutaneously (s.c.) administered clonidine (1 mg/kg) in a dose-dependent manner. The attenuating effect of muscimol (62.5 ng/mouse, i.c.v.) on the clonidine-induced antinociception was significantly blocked by the GABA a antagonists bicuculline (100–400 ng/mouse, i.c.v.) and picrotoxin (250 ng/mouse, i.c.v.) but not by the GABA B antagonist 2-hydroxysaclofen (10 μg/mouse, i.c.v.). On the other hand, the attenuating effect of R(+)-baclofen (50 ng/mouse, i.c.v.) was blocked by the coadministration with 2-hydroxysaclofen (20 μg/mouse), but was not affected by the coadministration with bicuculline (400 ng/mouse). These results indicate that both supraspinal GABA a and GABA b receptors play inhibitory roles in the antinociception caused by systemically administered clonidine.