Opioid induced non-photic phase shifts of hamster circadian activity rhythms

The phase of the circadian pacemaker in hamsters can be shifted by the application of certain non-photic stimuli late in the subjective day. A projection from the intergeniculate leaflet of the thalamus to the circadian pacemaker in the suprachiasmatic nucleus is believed to mediate some types of non-photic phase-shifting stimuli. In hamsters, this projection is immunoreactive to both Neuropeptide Y and enkephalin. Previous work in other laboratories has shown that Neuropeptide Y administration is capable of phase shifting circadian rhythms without the application of light. The present study was undertaken to determine if enkephalinergic compounds likewise have the ability to non-photically phase shift hamster activity rhythms. Hamsters were maintained under conditions of constant darkness and circadian wheel running activity was recorded. Agonists and antagonists selective for kappa, mu, and delta opioid receptors were systemically applied without light to hamsters at circadian times 8 and 10 to determine if they were able to elicit phase shifts in wheel running activity rhythms. Of the compounds tested, only the delta opioid agonist BW373U86 significantly affected circadian phase. BW373U86 phase advanced hamster wheel running activity rhythms by approximately 45 min, although total activity levels following drug application were not significantly affected. Changes in the amount of wheel running activity were detected after administration of some mu and kappa opioids, although the circadian phase was not altered. These results indicate that enkephalin-mimetic delta opioid agonists are capable of producing non-photic phase shifts in hamster activity rhythms, and that opioids can independently affect circadian phase and activity levels in hamsters.