Abstract
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 μg) 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.
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