Intrathecal Pertussis Toxin but not Cyclic AMP Blocks Kappa Opioid-Induced Antinociception in rat

The role of inhibitory G-proteins and cyclic AMP in spinal mechanisms of kappa opioid receptor-mediated an-tinociception was assessed by recording the withdrawal response latency of the rat tail following immersion into a water bath of 49d`C. Intrathecal administration of pertussis toxin (1 μg/rat, five days before the behavioral evaluation) prevented the antinociceptive effect of the kappa receptor agonist U-50,488H, while administration of dibutyryl cyclic AMP (10 μg/rat, 17 min. after U-50,488H) did not antagonize the antinociceptive action of the kappa ligand. Results suggest that in the spinal cord the signal transduction mechanism subserving the antinociceptive effect of U-50, 488H involves a Gi or Go protein, but also that cyclic AMP is not implicated in coupling Gi/Go proteins to the effector system.