KAPPA-3 OPIATE RECEPTOR-BINDING IN THE MOUSE AND RAT

Previous work examining the binding of [H-3]naloxone benzoylhydrazone (NalBzoH) in calf brain has identified a novel binding site, kappa-3. In mice and rats NalBzoH elicits an analgesic response which can clearly be differentiated from classical-mu, delta or kappa-1 mechanisms and which is pharmacologically consistent with a kappa-3 receptor mechanism of action. In the current studies we demonstrate the presence of kappa-3 sites in both mouse and rat brains. The selectivity of the kappa-3 sites for opioids clearly discriminated it from traditional-mu, kappa-1, kappa-2 or delta-receptors. In the rat, the density of kappa-3 sites increased 2.5-fold from age 2 days to 21 days, after which it remained relatively stable. Among a number of brain regions in the rat, the density of kappa-3 sites varied dramatically. Highest levels were present in the hypothalamus, thalamus, striatum and midbrain with very low levels in the cerebellum. Intermediate levels were present in cortex, brain stem and spinal cord. Together, these studies support the presence of kappa-3 receptors in both mouse and rat brain which are very similar to those previously reported in calf brain.