title: Methamphetamine and dopamine receptor D1 regulate entrainment of murine circadian oscillators.
abstract: We investigated the effect of methamphetamine (MA) injections on the circadian organization of behavior and individual tissues in the mouse. Scheduled, daily injections of MA resulted in anticipatory activity, with an increase in locomotor activity immediately prior to the time of injection. Daily MA also shifted the peak time of PER2 expression in the liver, pituitary, and salivary glands. It has been suggested that reward pathways, and dopamine signaling in particular, may underlie the effects of MA on the circadian system. To test this hypothesis, we examined the effect of the D1 receptor antagonist SCH23390 (SCH) on circadian rhythms. The MA-induced shift in the phase of pituitary and salivary glands was attenuated by pretreatment with the D1 antagonist SCH23390 (SCH). Interestingly, daily SCH, administered alone, also affected some circadian oscillators. The livers and lungs (but not pituitaries or salivary glands) of mice treated with daily injections of SCH displayed disrupted rhythms of PER2 expression, suggesting that D1 receptor signaling is important for entrainment of these organs. From these results, we conclude that MA has widespread effects within the circadian system, and that these effects are mediated, at least in part, by the dopaminergic system. This study also identifies a role for dopamine signaling in normal entrainment of circadian oscillators.
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Mohawk
authors.forename: Pinar
authors.initials: P
authors.lastname: Pezuk
authors.forename: Michael
authors.initials: M
authors.lastname: Menaker
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D001552:Benzazepines; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D008694:Methamphetamine