Morphine preexposure attenuates the aversive properties of opiates without preexposure to the aversive properties.

Evidence that action on peripheral opiate receptors is necessary to produce aversive effects with morphine, enabled us to determine whether preexposure to these aversive effects is necessary for the later attenuation of morphine's aversive properties. We found that blockade of the aversive effects of morphine with the peripheral antagonist methylnaltrexone during morphine preexposure had no effect on the later attenuated development of conditioned taste aversions to morphine. Moreover, in the same rat morphine preexposure did not affect the development of a place preference to an environment paired with injections of morphine. The results suggest that an effect of central opiate action is able to attenuate the later peripheral aversive, but not the central rewarding, effects of morphine.