Aripiprazole advances delayed sleep-wake rhythm in methamphetamine-treated mice

Area of Science:

• Neuroscience
• Chronobiology
• Pharmacology

Background:

• Circadian rhythm sleep-wake disorders (CRSWD) involve misalignment with the environment, often inadequately treated by melatonin or light therapy.
• Internal desynchronization, where circadian and sleep-wake rhythms dissociate, may underlie CRSWD in some patients, even with normal melatonin rhythms.
• Aripiprazole (APZ), a dopamine D2/D3 receptor partial agonist, has shown recent promise for CRSWD treatment.

Purpose of the Study:

• To investigate the efficacy of Aripiprazole (APZ) in a mouse model of CRSWD.
• To explore APZ's effects on sleep-wake rhythm synchronization and sleep architecture.

Main Methods:

• Male C57/Black6 mice were used to model CRSWD.
• APZ was administered to mice with normal sleep-wake rhythms and to chronic methamphetamine-treated mice exhibiting CRSWD-like phenotypes.
• Sleep-wake patterns and sleep architecture were monitored.

Main Results:

• APZ administration increased sleep during rest and wakefulness during the active period in mice with normal rhythms.
• In mice with CRSWD-like phenotypes, APZ synchronized the sleep-wake rhythm to the light-dark cycle.
• APZ treatment also altered sleep architecture in the CRSWD model.

Conclusions:

• Aripiprazole demonstrates potential in re-synchronizing disrupted sleep-wake rhythms in a mouse model of CRSWD.
• APZ may be effective for CRSWD patients experiencing internal desynchronization.
• These findings provide insights into APZ's mechanism of action for treating CRSWD.