Intermittent cold water stress-analgesia in rats: Cross-tolerance to morphine

Abstract

Continuous cold water swim (CCWS, 3.5 min, 2°C) induces a non-opiate type of analgesia since 14 mg/kg of naltrexone or 20 mg/kg of naloxone only partially antagonize this stress-induced analgesia (SIA) and since there is no cross-tolerance between CCWS and morphine-analgesia. Intermittent cold water swim (ICWS) analgesia is significantly antagonized by naltrexone (14 mg/kg). These studies suggested that CCWS-analgesia is mediated by non-opioid systems, while ICWS-analgesia acts through a system that also mediates morphine analgesia. The hypothesis that ICWS-analgesia shares a common opioid pathway with morphine-analgesia, but not with CCWS-analgesia, was further tested by cross-tolerance studies in rats. The results showed a complete cross-tolerance to morphine analgesia in ICWS-tolerant animals, but no cross-tolerance to ICWS-analgesia in morphine-tolerant animals. This suggests that morphine- and ICWS-analgesia partially share a common pathway, ICWS acting probably at levels “downstream” from the opiate-sensitive sites, while CCWS induces analgesia by acting on a different system which is not mediated by opioids.