Tolerance and cross tolerance with morphine resulting from physiological release of endogenous opiates.

Mice which had been exposed to a chronic schedule of warm water swimming showed the development of a significant tolerance to the antinociceptive response (tail-flick latency) and a significant, two-fold increase in the ED50 of morphine (tail-flick latency and abdominal constriction response). These results suggest the involvement of endogenous opiates during swim stress in mice and are consistent with the hypothesis that during chronic stress the opiate receptors are activated in a manner analogous to the repeated application of exogenous opiates producing tolerance, morphine cross tolerance and (as previously reported) withdrawal-like behaviour.