Nguyen T T, Matsumoto K, Watanabe H
Department of Pharmacology, Research Institute for Wakan-Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Life Sci. 1997;61(11):1097-103. doi: 10.1016/s0024-3205(97)00618-8.
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 microg/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 microg/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.
