Investigating the Anxiety-Increasing Potential of β-Carboline (FG-7142) in Zebrafish

Abstract

β-Carboline (FG-7142) is a partial inverse agonist of the benzodiazepine allosteric site at the GABA-A receptor. It has been shown to yield anxiety-increasing (anxiogenic), proconvulsant, and appetite-reducing effects among various aquatic and mammalian species, including humans. It is found naturally in succulents, hallucinogenic plants, as well as tobacco leaves, and may be made endogenously. While previous literature has focused on seizure-inducing effects, interest is growing in the anxiogenic effects it has on terrestrial and aquatic species to model high-anxiety states. This study aimed to (1) establish a dose response curve for anxiety-like behaviour in zebrafish and (2) evaluate FG-7142 in a conditioned fear paradigm. An open field test and novel object approach test were used to generate a dose response curve of FG-7142 on anxiety-like behaviours. A U-shaped distribution curve was found with peak responses in increased immobility, lowered velocity, and lowered distance travelled at 10.0 μM. These findings suggest that FG-7142 has a significant effect on some behavioural markers of increased anxiety. Currently, this effective dose of 10.0 μM is being used to evaluate fear and anxiety conditioning in zebrafish using a 3-day repeated exposure and subsequent submerged plus maze paradigm based on red-green colour preference. Should FG-7142 have a mediating effect in the formation of conditioned fear and anxiety responses, it is expected that zebrafish in this test should avoid locations in the plus maze associated with the colour that was present during their respective repeated exposures.

Faculty Mentor: Dr. Trevor Hamilton