Blockade of cannabinoid-induced antinociception by naloxone benzoylhydrazone (NalBZH)

We have recently shown that the antinociceptive effects, but not other behavioral effects of the intrathecally administered, but not intracerebroventricularly administered, cannabinoids, are blocked by the kappa antagonist, nor-binaltorphimine. We employed naloxone benzoylhydrazone, a kappa3 agonist, and kappa1, mu, and delta antagonist, to better characterize the interaction of cannabinoids with kappa receptors. Naloxone benzoylhydrazone blocked the antinociceptive effects of both intrathecally and intracerebroventricularly administered cannabinoids. Because the cannabinoids are not blocked by mu and delta antagonists, the effects of naloxone benzoylhydrazone are presumed to occur through interaction with kappa receptors. Because the data indicate that naloxone benzoylhydrazone does not block kappa3 receptors, the data indicate that the cannabinoids may interact with kappa1 receptors in the production of antinociception. However, differences in the profile of activity of naloxone benzoylhydrazone and the cannabinoids at kappa receptors exist. Thus, the exact nature of the interaction of the cannabinoids and the kappa receptors to be elucidated.