Dexmedetomidine elicits a prolonged anxiolytic effect by inhibiting adrenergic neurons in the locus coeruleus in mice.

ABSTRACT: Anxiety disorders impose a substantial global burden, yet current pharmacotherapies often lack sustained efficacy and carry risks of dependence. Dexmedetomidine (Dex), a selective α2 adrenergic receptor agonist primarily used for sedation, demonstrates promising anxiolytic properties, but its long-term neural mechanisms remain unclear. Here, using a chronic restraint stress (CRS) mouse model, we reveal that tyrosine hydroxylase (TH)-positive neurons in the locus coeruleus (LC) are persistently hyperactivated during chronic anxiety states, driving elevated norepinephrine (NE) release in the medial prefrontal cortex (mPFC). A single low dose of Dex (50 µg/kg) produced anxiolytic effects lasting ≥3 days, evidenced by improved performance in open-field, light-dark box, and elevated plus maze t

SUBMITTER: Jiang L 

PROVIDER: S-EPMC12627444 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature