Sex, drugs, and zebrafish: Acute exposure to anxiety-modulating compounds in a modified novel tank dive test

Abstract

This study investigated the effects of anxiogenic and anxiolytic drugs on zebrafish (Danio rerio) behaviour using a modified novel tank dive test with higher walls and a narrower depth. Zebrafish were administered chondroitin sulfate, beta-carboline, delta-9-tetrahydrocannabinol (THC), ethanol, and beta-caryophyllene, and their behaviours were evaluated for geotaxis, swimming velocity, and immobility. Both anxiogenic and anxiolytic compounds generally increased bottom-dwelling behaviour, suggesting that the tank's modified dimensions significantly influence zebrafish responses. EC₅₀ values for ethanol showed a lower threshold for velocity reduction compared to zone preference. Chondroitin sulfate uniquely caused a sex-specific increase in male swimming velocity, whereas no other sex-differences were observed with any compound. Interestingly, the presence of drug-treated fish did not alter the behaviour of observer fish, suggesting limited social buffering effects. The findings underscore the complexity of zebrafish behavioural phenotypes and highlight the need for considering tank dimensions and multiple behavioural parameters to accurately assess the effects of anxiety-modulating drugs. This study demonstrates the utility of the modified novel tank dive test in providing nuanced insights into the behavioural effects of different pharmacological agents in zebrafish.