Morphine phase-shifts circadian rhythms in mice: role of behavioural activation

The effect of morphine on circadial wheel-running rhythms of C57BL/6j mice was examined. Mice received morphine (25 mg kg-1, i.p.) or saline at eight different circadian phases in constant dark. Morphine injections in the middle of the inactive period induced significant advance phase shifts, whereas injections at other times induced small delay shifts or no responses. This phase-response relationship was not altered by optic enucleation. Morphine also induced hyperactivity. Restriction of activity prevented phase shifts. The results indicate that morphine shifts circadian rhythms by its effects on behaviour, rather than by a direct action on the circadian pacemaker. Morphine may represent a useful tool for further study of behaviourally induced phase-resetting in this species.