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Methamphetamine and dopamine receptor D1 regulate entrainment of murine circadian oscillators

Jennifer A Mohawk1, Pinar Pezuk, Michael Menaker

  • 1Department of Biology, University of Virginia, Charlottesville, Virginia, United States of America.

Plos One
|April 30, 2013
PubMed

Insights

Methamphetamine disrupts circadian rhythms in mice, affecting behavior and tissue clocks. Dopamine signaling plays a key role in these methamphetamine-induced effects and normal circadian entrainment.

Area of Science:

  • Chronobiology
  • Neuropharmacology
  • Molecular Biology

Background:

  • Methamphetamine (MA) is known to affect behavior and reward pathways.
  • Dopamine signaling is implicated in the central nervous system's response to MA.
  • Circadian rhythms govern physiological processes, including behavior and gene expression in peripheral tissues.

Purpose of the Study:

  • To investigate the impact of methamphetamine on the circadian organization of behavior and peripheral tissues in mice.
  • To determine the role of dopamine D1 receptor signaling in mediating MA's effects on circadian rhythms.
  • To explore the involvement of dopamine signaling in the normal entrainment of circadian oscillators.

Main Methods:

  • Daily administration of methamphetamine (MA) to mice to assess behavioral changes and PER2 gene expression rhythms.
  • Utilized the D1 receptor antagonist SCH23390 (SCH) to investigate the role of dopaminergic pathways.
  • Measured PER2 expression in the liver, pituitary, and salivary glands to assess circadian phase shifts.

Main Results:

  • Daily MA injections induced anticipatory activity and shifted PER2 expression peaks in the liver, pituitary, and salivary glands.
  • Pretreatment with SCH23390 attenuated MA-induced phase shifts in the pituitary and salivary glands.
  • SCH23390 alone disrupted PER2 rhythms in the liver and lungs, indicating a role for D1 signaling in peripheral circadian entrainment.

Conclusions:

  • Methamphetamine exerts widespread effects on the mammalian circadian system, mediated partly by the dopaminergic system.
  • Dopamine D1 receptor signaling is crucial for the normal entrainment of circadian rhythms in specific organs like the liver and lungs.
  • This study highlights the intricate relationship between drug-induced neurochemical changes and the regulation of biological clocks.

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