Involvement of supraspinal GABA-ergic systems in clonidine-induced antinociception in the tail-pinch test in mice.
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.
Nguyen
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TT
Department of Pharmacology, Research Institute for Wakan-Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Matsumoto
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K
Watanabe
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H
D058647:Adrenergic alpha-2 Receptor Agonists; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D010852:Picrotoxin / Q000494:pharmacology; D018079:Receptors, GABA / Q000502:physiology*; D013623:Tail; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D058647:Adrenergic alpha-2 Receptor Agonists; D000700:Analgesics; D001418:Baclofen; D001640:Bicuculline; D003000:Clonidine; D018756:GABA Antagonists; D009118:Muscimol; D010852:Picrotoxin; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; C057491:2-hydroxysaclofen