Anxiolytic-like Effect in Adult Zebrafish (Danio rerio) through GABAergic System and Molecular Docking Study of Chalcone (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one

Benzodiazepines are used to treat anxiety disorders. The chronic use of these drugs can cause tolerance or relevant adverse effects, requiring the search for new, safer, and more effective compounds. In this context, the present work aimed to investigate the potential anxiolytic effect of the chalcone synthesized and its mechanism of action, using the adult zebrafish (Zfa) as an animal model. The animals were treated with the new chalcone (4.0; 20 and 40.0 mg/kg) in the 96h open field and toxicity test. The concentrations that caused locomotor alteration were evaluated in the light and dark anxiolytic test, with the lowest active dose being used to assess the mechanism via the GABAergic system. The chalcone proved to be safe compared to the adult Zebrafish model up to 96h of analysis and caused locomotor alteration of Zfa similar to that of benzodiazepines. The chalcone presented an anxiolytic effect, which was blocked by flumazenil, a GABAA receptor antagonist, thus demonstrating that the chalcone must act via the mechanism of the GABA system. In this perspective, chalcone has the potential to be used as a pharmacological tool in the treatment of anxiety disorders.