Blockade of the development of analgesic tolerance to morphine by concurrent treatment with opioid-but not non-opioid-mediated stress in mice.

Studies have been carried out to determine how the analgesic effect of morphine and the development of tolerance to the effect would be influenced by concurrent exposure to stresses in mice. Application of footshock (FS) stress, which produces analgesia mediated by opioid mu-receptors, or psychological (PSY) stress, which produces analgesia in a manner more closely related to opioid kappa-receptors, did not affect the analgesic effect of morphine, but completely blocked the development of tolerance during 5 daily concomitant treatments. On the other hand, forced swimming (SW) stress induced analgesia (SIA), which was not antagonized by naloxone, suppressed morphine analgesia, but failed to block the tolerance development. The blockade of the development of tolerance to morphine analgesia by stresses may not be attributed to the analgesic effect induced by the stresses because a combination of weak FS stress, which induces no analgesia, also effectively suppressed the development of morphine tolerance. In addition to the opioid mechanism, an adrenergic mechanism can not be excluded because of the reserpine antagonism of these SIAs.