High-fat diet-induced dopaminergic dysregulation induces REM sleep fragmentation and ADHD-like behaviors

Consumption of a high-fat diet (HFD) has been associated with reduced wakefulness and various behavioral deficits, including anxiety, depression, and anhedonia. The dopaminergic system, which plays a crucial role in sleep and ADHD, is known to be vulnerable to chronic HFD. However, the association between HFD-induced behavioral and molecular changes remains unclear. Therefore, we investigated the effects of a HFD on the dopaminergic system and its association with behavioral deficits in male mice. The mice were divided into normal diet and HFD groups and were analyzed for sleep patterns, behavior tests, and transcription levels of dopamine-related genes in the brain. The HFD group showed decreased wakefulness, increased REM sleep with fragmented patterns, decreased time spent in the center zone of the open field test, shorter immobile time in the tail suspension test, impaired visuospatial memory, and reduced sucrose preference. Additionally, the HFD group had decreased mRNA levels of D1R, COMT, and DAT in the nucleus accumbens, which negatively correlated with REM sleep proportion and REM sleep bout count. The results suggest that HFD-induced behavioral deficits were resemblance to ADHD-like behavioral phenotypes and disturbs REM sleep by dysregulating the dopaminergic system.