Anxiolytic-Like Effect of Chrysin on Female Zebrafish is Likely Mediated by α 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 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.