Morphine dependence with or without tolerance in formalin-treated mice: further evidence for the dissociation.

Pain associated-anxiety induced by formalin, which resulted in a significant delay in the development of tolerance to morphine antinociception, failed to prevent the development of physical dependence as evidenced by naloxone challenge. Dependence also developed in mice rendered tolerant to morphine. Thus, the development of morphine dependence was observed in the absence and presence of tolerance to morphine antinociception; Our results further confirm the dissociation of opioid tolerance and dependence in the animal model of experimental pain/anxiety.