Phase-dependent phase shift of methamphetamine-induced circadian rhythm by haloperidol in SCN-lesioned rats.
Haloperidol, a non-selective dopamine receptor antagonist, was injected intraperitoneally in to suprachiasmatic nucleus (SCN)-lesioned rats at various phases of the locomotor activity rhythm induced by methamphetamine (MAP) treatment. A single injection of haloperidol shifted the phase of MAP-induced locomotor rhythm phase dependently, while saline injection had no effect on the phase. A phase-response curve of MAP-induced rhythm for haloperidol had a small phase-advancing area at CT 13 to 15, a large phase-delaying area at CT 3 to 7 and a dead zone at CT 17 to 1. Although the day-to-day variation of MAP-induced locomotor rhythm was about 2.5-times as great as that of light entrainable circadian rhythm, the phase shifts of both directions were statistically significant. Phase delay shifts at CT 5 depended on the dose of haloperidol. In addition to the phase-shifting effect, haloperidol suppressed the MAP-induced locomotor activity for activity for about 10 h regardless of the phase of the injection. Pentobarbital also suppressed ther locomotor activity for a similar duration. However, significant phase shift was not detected with pentobarbital injected at CT 5 or CT 13, at the phase where haloperidol induced the maximal phase delay or advance, respectively. Present findings suggest that the dopaminergic mechanism is involved in the entrainment and/or oscillatory mechanism of the MAP-induced rhythm.
Honma
S
S
Department of Physiology, Hokkaido University School of Medicine, Sapporo, Japan.
Honma
K
K
D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D008694:Methamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013493:Suprachiasmatic Nucleus / Q000033:anatomy & histology / Q000502:physiology*
D008694:Methamphetamine; D010424:Pentobarbital; D006220:Haloperidol