Differential Behavioral Responses of Zebrafish Larvae to Yohimbine Treatment

Rationale: Yohimbine demonstrated both anxiogenic and anxiolytic properties under different conditions in rodents. Few studies were conducted on zebrafish, a newly emerged vertebrate model organism. Zebrafish larvae are particularly suitable for high-throughput screening of drug effects.

Objectives: The aim of this study was to elucidate the effect of yohimbine on the anxiety-related behaviors of zebrafish larvae.

Methods: AB strain zebrafish larvae at both 5 and 7 days postfertilization (dpf) were treated with different concentrations of yohimbine. General locomotor activities and thigmotaxis behavior were analyzed under continuous illumination, which represented normal condition, or under alternating light-dark challenges, which represented stressful environment.

Results: Under continuous illumination, the 5-dpf larvae demonstrated increased swimming distances at low yohimbine concentrations, whereas the 7-dpf larvae demonstrated progressively decreased swimming distances with increases in yohimbine concentration. Low concentrations of yohimbine reduced thigmotaxis of the larvae, while high concentrations of yohimbine increased it. During the dark period of the light-dark challenge phase, low concentrations of yohimbine increased swimming distances of the larvae at both 5 and 7 dpf, while high concentrations of yohimbine decreased it. Yohimbine induced increased thigmotaxis in both 5- and 7-dpf larvae during the dark period.

Conclusions: Under normal condition (lights on), low doses of yohimbine were anxiolytic in both the 5- and 7-dpf larvae, whereas high doses of yohimbine were anxiogenic only in the 7-dpf larvae. Under mildly stressful condition (lights off), yohimbine treatment demonstrated dose-dependent effects to potentiate anxiety-related behaviors in both the 5- and 7-dpf larvae, although the significant dose varied with age.