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.