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

No SJR dataFeb 2, 2026Chronobiology international

Aripiprazole helps reset delayed sleep patterns in mice treated with methamphetamine

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Aripiprazole increased sleep during rest periods and wakefulness during active periods in mice.

One-third or more of patients with circadian rhythm sleep-wake disorders may have normal melatonin rhythms.
The study indicates potential internal desynchronization in these patients, where circadian and sleep-wake rhythms do not align.
In male C57/Black6 mice, aripiprazole administration improved synchronization of sleep-wake rhythms to the light-dark cycle.
Chronic methamphetamine-treated mice with a sleep phenotype resembling CRSWD exhibited changes in sleep architecture following aripiprazole treatment.
Findings provide insights into the mechanisms by which aripiprazole may affect patients with CRSWD and internal desynchronization.

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Circadian rhythm sleep-wake disorders (CRSWD) are characterized by misalignment between the sleep-wake rhythm and the environmental day-night cycle, leading to disturbances in daily life. Melatonin and light therapy targeting circadian rhythms are generally used, but with limited efficacy. Recent studies have revealed that one-third or more of CRSWD patients with abnormal sleep-wake rhythm have normal melatonin rhythm, indicating the possible involvement of internal desynchronization, where circadian rhythm and sleep-wake rhythm dissociate. Aripiprazole (APZ) is a dopamine D2/D3 receptor partial agonist and has recently been shown effective to CRSWD. In this study, we explored the potential of APZ in treating mouse model of CRSWD. We use male C57/Black6 mice and first demonstrated APZ administered to the mice with normal sleep-wake rhythm increased sleep during the rest period and also increased wakefulness during the next active period. We next found APZ administered to the chronic methamphetamine (MAP)-treated mice with CRSWD like sleep phenotype synchronized their sleep-wake rhythm to the light-dark cycle. This entrainment was also accompanied by changes in sleep architecture. These findings brought insights into the mechanism how APZ acts on patients with CRSWD, especially with internal desynchronization.

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