Anxiolytic‐Like Effect of Chrysin on Female Zebrafish is Likely Mediated by α ₅ Subunits of γ‐Aminobutyric Acid A Receptors

Chrysin (5,7‐dihydroxyflavone) is a natural flavonoid with potential anxiolytic‐like effects in preclinical models. Acute treatment with this molecule (0–10 mg/kg) produced a biphasic dose‐response in the zebrafish light/dark test (LDT), with anxiolytic‐like effects at low doses and anxiogenic‐like effects at high doses. Chrysin (1 mg/kg) decreased anxiety‐like behavior in the zebrafish novel tank test but did not prevent the anxiogenic effects of acute stress. The anxiolytic‐like effects of chrysin (1 mg/kg) in the LDT were blocked by pretreatment with picrotoxin, suggesting interaction with γ‐aminobutyric acid A receptors. Molecular modeling suggested that chrysin interacts with α 5 subunits at residues lining the ion channel pore. These results demonstrate one of the possible mechanisms of action of chrysin, reinforcing the anxiolytic potential of this molecule.