The methamphetamine-sensitive circadian oscillator (MASCO) in mice

Area of Science:

• Chronobiology
• Neuroscience
• Pharmacology

Background:

• The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker.
• Methamphetamine (MAP) uniquely affects circadian behavior, suggesting an SCN-independent oscillator.
• The methamphetamine-sensitive circadian oscillator (MASCO) has been observed in rats, but its properties and location are unknown.

Purpose of the Study:

• To investigate the effects of chronic MAP on circadian locomotor activity in mice.
• To determine if an SCN-independent circadian oscillator exists and responds to MAP in mice.
• To characterize the properties of this extra-SCN oscillator in different mouse strains and conditions.

Main Methods:

• Chronic MAP administration to intact and SCN-lesioned mice of two strains.
• Experiments conducted in constant dark and constant light conditions.
• Varied MAP availability schedules in SCN-lesioned mice to assess circadian properties.

Main Results:

• A methamphetamine-sensitive circadian oscillator (MASCO) was identified in mice, operating independently of the SCN.
• The MASCO induces robust locomotor rhythmicity in SCN-lesioned mice, persisting after MAP withdrawal.
• MASCO-SCN interactions are strain, sex, and dose-dependent in intact mice.

Conclusions:

• The MASCO is a functional circadian pacemaker in mice, demonstrating circadian properties.
• This oscillator plays a significant role in regulating locomotor activity rhythms, even without the SCN.
• Future research should focus on localizing the MASCO and elucidating its molecular mechanisms and interactions.