Dexmedetomidine alleviates host ADHD-like behaviors by reshaping the gut microbiota and reducing gut-brain inflammation

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders that affects children and even continues into adulthood. Dexmedetomidine (DEX), a short-term sedative, can selectively activate the alpha 2-adrenoceptor. Treatment with alpha 2-adrenergic agonists in patients with ADHD is becoming increasingly common. However, the therapeutic potential of DEX for the treatment of ADHD is unknown. Here, we evaluated the effect of DEX on ADHD-like behavior in spontaneously hypertensive rats (SHRs), a widely used animal model of ADHD. DEX treatment ameliorated hyperactivity and spatial working memory deficits and normalized theta electroencephalogram (EEG) rhythms in SHRs. We also found that DEX treatment altered the gut microbiota composition and promoted the enrichment of beneficial gut bacterial genera associated with antiinflammatory effects in SHRs. The gut pathological scores and permeability and the level of inflammation observed in the gut and brain were remarkably improved after DEX administration. Moreover, transplantation of fecal microbiota from DEX-treated SHRs produced effects that mimicked the therapeutic effects of DEX administration. Therefore, DEX is a promising treatment for ADHD that functions by reshaping the composition of the gut microbiota and reducing inflammation in the gut and brain.

Automated summary

Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder that affects children and continues into adulthood. Dexmedetomidine (DEX), a short-term sedative, has shown potential as a treatment for ADHD by improving ADHD-like behavior and normalizing brain rhythms in an animal model of ADHD. DEX treatment also alters the gut microbiota and reduces inflammation in the gut and brain, suggesting its therapeutic effects are mediated by reshaping the gut microbiota.