OPIOID AND SUBSTANCE-P RECEPTOR ADAPTATIONS IN THE RAT SPINAL-CORD FOLLOWING SUBCHRONIC INTRATHECAL TREATMENT WITH MORPHINE AND NALOXONE

The effect of continuous intrathecal infusion with morphine (5 mu/h) o r naloxone (2 mug/h) was investigated with regard to analgesia and the apparent density of mu- and delta-opioid and neurokinin-I/substance P receptors in the rat spinal cord. Morphine infusion increased tail-fl ick and paw-pressure responses until day 4 after the mini-osmotic pump implant. A decline in antinociception, reflecting tolerance to morphi ne, was then apparent in both tests. Quantitative in vitro receptor au toradiography of [I-125]FK-33824, [I-125][D.Ala2]deltorphin-I and [I-1 25] Bolton-Hunter substance P binding sites, as ligands of mu, delta a nd neurokinin-I/substance P receptors, respectively, was performed on lumbosacral spinal cord sections of seven-days tolerant animals. Treat ments with morphine and naloxone induced a similar increase (37%) in t he number of delta binding sites in the superficial laminae of the dor sal horn. In contrast, the density of mu-opioid receptors was only aff ected by naloxone (50% increase). Neurokinin-I/substance P binding par ameters were not altered by these treatments. Thus, it appears that de lta-opioid binding sites may be of special relevance with regard to th e development of tolerance to opiates in the spinal cord.