Anxiolytic-like and Anticonvulsant Effect in Adult Zebrafish (Danio rerio) through GABAergic System and Molecular Docking Study of Chalcone Derived from Natural Products

Abstract

Anxiety and seizure are mental disorders commonly treated in the clinic with benzodiazepines (BZDs). However, long-term treatment with these drugs causes side effects such as decreased motor coordination, drowsiness, sedation, and, when used for a long time, leads to dependence and withdrawal syndromes. This study's objective was to evaluate the anxiolytic-like and anticonvulsant effect in adult zebrafish (Danio rerio) through GABAergic system of synthetic chalcone derived from cinnamaldehyde and natural acetophenone isolated from Croton anisodontus and their mechanisms of action via the Gabaergic system, using adult zebrafish. The animals were treated with chalcone (0.1 or 0.5 or 1.0 mg / kg; 20 µL; i.p;) and subjected to the open field test. The chalcone caused locomotor alteration when evaluated in the light & dark anxiolytic test. The lowest effective dose was chosen to assess possible involvement in the GABAA receptor. The chalcone showed anxiolytic and anticonvulsant effects in all doses in both tests. The chalcone presented anticonvulsant activity, a possible inhibitor of Carbonic Anhydrase and an anxiolytic effect dependent on the GABAergic system, coupling it in a different region from the diazepam inhibitor.