Heterocyclic Hydroxychalcone Promotes Anxiolytic and Anticonvulsant Effects through Gabaergic Neuromodulation in Wild Adult Zebrafish

Benzodiazepines are drugs used to treat anxiety disorders and epilepsy due to their hypnotic, anxiolytic and anticonvulsant functions. But due to existing adverse effects such as decreased psychomotor activity and impaired memory, new and safer drugs are sought. Therefore, this study seeks to evaluate the anxiolytic and anticonvulsant action of chalcone (E)-3-(furan-2-yl)-1-(2-hydroxyphenyl)prop-2-en-1-one against wildadult zebrafish, and the mechanisms of action involved in such effects.The acute toxicity of chalcone was analyzed during 96 hours, and the anxiolytic behavior of fish treated with chalcone was evaluated in light/dark tests and open field tests (n=6 animals/group). In the test to evaluate the anticonvulsant effect of the sample, Pentylenetetrazole (PTZ) was used to induce seizures by immersion. Next, we investigated the mechanism of action with the γ-aminobutyric acid (GABA) antagonist and performed a molecular coupling study. The results showed that chalcone at doses of 4, 20, and 40 mg/kg was non-toxic and altered fish locomotion (****p<0.0001 vs. control). All analyzed doses exhibited possible anxiolytic effects (* p < 0.05, *** p < 0.001 vs. control) in the light/dark test. This effect was blocked by the antagonist flumazenil (FMZ) at a dose of 40 mg/kg (# p < 0.05 vs. Fmz+Chalcone). In addition to exhibiting anxiolytic effects, chalcone demonstrated anticonvulsant effects via GABA, as confirmed by a binding/activity study (### p < 0.01, #### p < 0.0001 vs. Fmz+Chalcone).