Fentanyl, but not haloperidol, entrains persisting circadian activity episodes when administered at 24- and 31-h intervals.

Administration of several drugs of abuse on a 24-h schedule has been shown to entrain both pre-drug (anticipatory) and post-drug (evoked) circadian activity episodes that persist for several days when the drug is withheld. The present study tested the entrainment effects of fentanyl, an opioid agonist with a noted abuse liability, and haloperidol, an anti-psychotic dopamine antagonist without apparent abuse liability. Adult female Sprague-Dawley rats housed under constant light in cages with attached running wheels received repeated low, medium, or high doses of either fentanyl or haloperidol on a 24-h administration schedule followed by a 31-h schedule (Experiment 1) or solely on a 31-h schedule (Experiment 2). The results showed that all three doses of fentanyl entrained both pre-drug and post-drug episodes of wheel running when administered every 24h, and the combined pre- and post-fentanyl activity episodes persisted for at least 3 days when the drug was withheld during test days. On the 31-h schedule, fentanyl produced an "ensuing" activity episode approximately 24h post-administration, but failed to produce an anticipatory episode 29-31h post-administration. In contrast, haloperidol injections failed to produce both pre-drug episodes on the 24-h schedule and circadian ensuing episodes on the 31-h schedule, and post-haloperidol suppression of activity appeared to mask the free-running activity rhythm. Taken together, these results provide additional evidence that drugs of abuse share a common ability to entrain circadian activity episodes.