Methamphetamine and dopamine receptor D1 regulate entrainment of murine circadian oscillators

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 M...

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Published in:PloS one Vol. 8; no. 4; p. e62463
Main Authors: Mohawk, Jennifer A, Pezuk, Pinar, Menaker, Michael
Format: Journal Article
Language:English
Published: United States Public Library of Science 23-04-2013
Public Library of Science (PLoS)
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Summary: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.
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Current address: Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
Conceived and designed the experiments: JAM PP MM. Performed the experiments: JAM PP. Analyzed the data: JAM PP. Wrote the paper: JAM PP MM.
Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0062463