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 24 h, 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 24 h post-administration, but failed to produce an anticipatory episode 29–31 h 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.