Evaluation of Anxiolytic Effect of Trans-Ferulic Acid in Zebrafish

Abstract

Background: Anxiety disorders are on the rise and current anti-anxiety drugs like benzodiazepines and SSRIs (selective serotonin reuptake inhibitors) use are associated with lots of adverse drug reactions including tolerance, suicidal tendency especially on chronic use. Thus, there is a need for identification of newer anti-anxiety drugs. Zebrafish recently gained attraction as an animal model. The present study aimed to evaluate the anxiolytic effect of trans-ferulic acid in zebrafish.

Methods: This study was conducted in zebra fish in the animal house of our institute. Animals were divided into 7 groups, 10 fish in each group with the sample size of 350. Anxiolytic effect of trans ferulic acid was studied using five tests i.e., Novel tank test, Light dark preference test, Acute stress test, Mirror biting test and Social preference test. Study was initiated after approval of Institutional Animal Ethics Committee (IAEC), and the experiment was done as per The Committee for Control and Supervision of Experiments on Animals (CCSEA) guidelines and Good Laboratory practice.

Results: Our study showed that in novel tank test, zebra fishes treated with fluoxetine, clonazepam and trans-ferulic at doses of 150mg/L ,300mg/L and 450mg/L (274.9 ± 26.5 vs 124.3 ± 7.11 vs 131.1 ± 16.37 vs 138 ± 19.66 vs 170.3 ± 21.55⁾ spent more time (sec) in upper zone compared to those fishes with distilled water (42.7 ± 8.6) or ethanol (45.9 ± 5.73).

In light dark preference test, zebra fishes treated with clonazepam (208.8 ± 27.72), fluoxetine (186.9 ± 37.09), and trans-ferulic acid 450mg/L (200.7 ± 20.51) spent more time in the light compartment compared to the distilled water (47.9 ± 16.52) or ethanol (95.2 ± 13.06). Also, zebra fishes treated with trans-ferulic acid at doses of 150mg/L and 300 mg/L (149.9 ± 14.66 vs 164.9 ± 18.96) spent more time(sec) in light compartment compared to those treated with distilled water (47.9 ± 16.52).

In acute stress test similar to novel tank test, Zebrafishes treated with Fluoxetine (305.30 ± 19.06), clonazepam (144.20 ± 26.43) and trans-ferulic acid 150mg/L, 300mg/L and 450mgL (114.40 ± 9.04 vs 153.20±35.37 vs 238.00 ± 34.90) spent more time (sec) in the upper zone compared to distilled water (60.80±7.44) or ethanol (55.70 ± 16.09).

In mirror biting test, Zebrafishes treated clonazepam (12.30±3.66), trans-ferulic acid 300mg/L (12.30 ± 1.87) and 450mg/L (9.00 ± 1.70) showed less number of mirror contacts compared to the distilled water (40.90 ± 13.89)

In social preference test zebra fish treated with trans-ferulic acid 300mg/L (27.50 ± 5.47) showed more number of entries in the empty arm compared to negative control (11.20 ± 3.26), vehicle control (9.70 ± 1.77), clonazepam (12.70 ± 2.31) and fluoxetine (4.5 ± 1.26).