Investigation of "cross-tolerance" between systemic and intrathecal morphine in rats.

Animals were implanted subcutaneously with morphine or placebo pellets and assessed daily on the hot plate or the tail flick test. After tolerance developed to morphine-induced analgesia the response to an acute systemic (1-6 mg/kg SC) or intrathecal morphine injection (0-30 micrograms) was determined. "Cross-tolerance" was observed on both the hot plate (6 mg/kg) and the tail flick tests (3 and 6 mg/kg) between the two different routes of subcutaneous administration. "Cross-tolerance" was also observed between systemic and intrathecal morphine on the hot plate test. However, no "cross-tolerance" between systemic and spinal morphine was observed in animals on the tail flick test. Assessment of naloxone-precipitated withdrawal indicated that morphine implanted animals showed more abstinence signs (wet shakes and teeth chattering) than placebo animals. These results suggest that the nociceptive assessment procedure plays a significant role in the expression of "cross-tolerance" between systemic and spinal opiates.