κ Opioid receptor-mediated analgesia in the developing rat

The prototypic κ opiate ketocyclazocine produced robust analgesia in 10-day-old rats in the tail-flick nociceptive test. The κ-opiate behavioral response coincided with the onset of a rapid rise to adult levels in brain κ receptor site density. In contrast, morphine (prototypic μ opiate) was without marked effect until 14 days of age. The period of rapid μ receptor increase did not take place until days 14-16, which was after κ receptor levels had already plateaued. Further, there was no or incomplete cross-tolerance between ketocyclazocine and morphine at 14 days of age. The present study, therefore, establishes a role for the κ binding site in thermal analgesia in the tail flick test and differentiates its ontogenetic pattern from that of the μ receptor.