Involvement of supraspinal GABA receptors in majonoside-R2 suppression of clonidine-induced antinociception in mice.
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 alpha2-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 alpha2-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 microg/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 microg/mouse) and the GABA(A) antagonist picrotoxin (0.25 microg/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.
Nguyen
T T
TT
Department of Pharmacology, Research Institute for Wakan-Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Matsumoto
K
K
Yamasaki
K
K
Watanabe
H
H
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000700:Analgesics / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005442:Flumazenil / Q000008:administration & dosage / Q000494:pharmacology; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology; D036145:Ginsenosides; D019329:Idazoxan / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D010147:Pain Measurement; D010852:Picrotoxin / Q000008:administration & dosage / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000502:physiology*; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology*; D013116:Spinal Cord / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D003000:Clonidine; D005442:Flumazenil; D018756:GABA Antagonists; D018757:GABA Modulators; D036145:Ginsenosides; D019329:Idazoxan; D010852:Picrotoxin; D011963:Receptors, GABA-A; D012503:Saponins; C098043:majonoside R2