Alpha 2 receptors mediate the antinociceptive action of 8-OH-DPAT in the hot-plate test in mice.
The prototypical 5-HT1A agonist, 8-OH-DPAT, dose-dependently (0.16-10.0 mg/kg, s.c.) elicited a pronounced antinociception in the hot-plate test in mice. This action was not affected by the 5-HT1A antagonists, BMY 7378, (-)-pindolol and (-)-alprenolol nor by selective antagonists at 5-HT1C, 5-HT2 and 5-HT3 receptors. It was also resistant to antagonists at D1, D2, alpha 1 and opioid receptors. In contrast, it was blocked by the alpha 2 antagonists, idazoxan, rauwolscine and yohimbine. L 659,066, a selective alpha 2 antagonist which does not enter the CNS, was ineffective. The action of 8-OH-DPAT was mimicked by the centrally acting alpha 2 agonists, UK 14,304 and guanabenz whereas ST 91, which does not penetrate the blood-brain barrier, was inactive. The action of UK 14,304 and guanabenz was also blocked by idazoxan, rauwolscine and yohimbine but not by L 659,066. These data indicate that the antinociceptive properties of 8-OH-DPAT in the hot-plate test in mice are mediated by CNS-localized alpha 2 receptors, rather than 5-HT1A receptors.
Millan
M J
MJ
Neurobiology Division, FONDAX, Paris, France.
Colpaert
F C
FC
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000700:Analgesics; D000818:Animals; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D011930:Reaction Time / Q000187:drug effects; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D015259:Dopamine Agents; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin