Methamphetamine and Dopamine Receptor D1 Regulate Entrainment of Murine Circadian Oscillators

Jennifer A Mohawk,Michael Menaker,Pinar Pezuk,Shizufumi Ebihara

doi:10.1371/journal.pone.0062463

Jennifer A Mohawk, Michael Menaker + Show 2 more

Open Access

https://doi.org/10.1371/journal.pone.0062463

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Journal: PloS one	Publication Date: Apr 23, 2013
Citations: 45	License type: CC BY 4.0

Affiliation: University of Virginia

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.

Highlights

Circadian rhythms, approximately 24h rhythms of behavioral and physiological processes, are regulated in mammals by a central pacemaker within the suprachiasmatic nucleus (SCN) of the hypothalamus [1,2]
While light is normally the strongest zeitgeber (‘‘time-giver’’) for the circadian system, keeping organisms entrained to the external environment, it is clear that other factors, including food and drugs, are capable of entraining the circadian system, and of driving rhythms in the absence of the SCN [3,4,5]
The stimulant drug of abuse methamphetamine has profound effects on circadian rhythms [6,7,8,9], but the way in which this drug interacts with the SCN to affect the brain and peripheral organs is not well understood

Summary

Introduction

Approximately 24h rhythms of behavioral and physiological processes, are regulated in mammals by a central pacemaker within the suprachiasmatic nucleus (SCN) of the hypothalamus [1,2]. Scheduled injections of MA reinstate behavioral circadian rhythms in otherwise arrhythmic SCN-lesioned animals [13] These rhythms persist on withdrawal days and are associated with a reinstatement of circadian rhythms of Per expression in the striatum and liver of the SCN-lesioned animals [13]. This suggests that the activity and clock gene expression rhythms driven by scheduled MA injections are SCNindependent. Given the ability of scheduled MA injections to influence clock gene expression in the brain and liver, we hypothesized that daily injections of MA in SCN-intact animals would shift the phase of other circadian oscillators in individual organs without affecting rhythms in the SCN

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