Involvement of supraspinal GABA receptors in majonoside-R2 suppression of clonidine-induced antinociception in mice

Abstract

Majonoside-R2 (MR2) is a major constituent of Vietnamese ginseng ( Panax vietnamensis, Ha et Grushv. Araliaceae) that is known to exhibit antagonistic activity against opioid-induced antinociception. In this study, we investigated the effect of MR2 on the antinociception caused in mice by the α2-adrenoceptor agonist clonidine, and elucidated the role of supraspinal GABAergic systems in this effect of MR2. The systemic administration of clonidine (0.5–2.5 mg kg , s.c.) dose-dependently suppressed the nociceptive response of mice in the tail-pinch and hot-plate tests. The intraperitoneal (i.p.), intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration of idazoxan (a selective α2-adrenoceptor antagonist) significantly antagonized the antinociceptive effect of clonidine in both tests. MR2 administered systemically (1.5–6.2 mg kg , i.p.) or centrally (5–10 μg/mouse, i.c.v. or i.t) dose-dependently antagonized the clonidine (1 mg kg , s.c.)-induced antinociception in the tail-pinch test but not in the hot-plate test. The antagonistic effect of i.c.v. MR2 on the systemic clonidine-induced antinociception in the tail-pinch test was significantly reversed by i.c.v. administrations of the selective benzodiazepine receptor antagonist flumazenil (5 μg/mouse) and the GABA A antagonist picrotoxin (0.25 μg/mouse). These results suggest that the supraspinal GABA A/benzodiazepine receptors are involved in the antagonistic effect of MR2 on the clonidine-induced antinociception in the tail-pinch test in mice.