Relative Involvement of Spinal Opioid Receptors in Physical Dependence on Intrathecal Butorphanol and Morphine

The present study was carried out to investigate the relative involvement of spinal opioid receptors in the development of physical dependence on intrathecal (IT) butorphanol in comparison with IT morphine. Dependence was induced by continuous IT infusion of butorphanol (52 nmol/h) and morphine (26 nmol/h) for 4 days in male Sprague–Dawley rats. Naloxone, CTOP, naltrindole, and nor-binaltorphimine (nor-BNI) were administered IT to precipitate behavioral signs of withdrawal. Administration of IT naloxone produced a significantly greater increase in the profile of withdrawal signs in IT morphine dependence than that in IT butorphanol dependence. An IT nor-BNI challenge elicits behavioral signs of withdrawal only in rats dependent on IT butorphanol, but not in rats dependent on IT morphine. CTOP administered IT precipitated withdrawal signs in IT morphine dependence that were greater than that in IT butorphanol dependence. An IT treatment with naltrindole produced equivalent signs of withdrawal in both IT butorphanol- and morphine-dependent rats. These results suggest that continuous IT butorphanol results in the development of less physical dependence than that of IT morphine. Spinal κ- rather than δ- and μ-opioid receptors play a major role in the development of IT butorphanol dependence, whereas spinal μ-opioid receptors play a more important role than δ-opioid receptors in IT morphine dependence.