Effects of anxiolytics in zebrafish: Similarities and differences between benzodiazepines, buspirone and ethanol

Abstract

There is growing interest in zebrafish as a model organism in behavioral pharmacology research. Several anxiety behaviors have been characterized in zebrafish, but the effect of anxiolytic drugs on these parameters has been scarcely studied. The purpose of this work was to assess the predictive validity of acute treatment with anxiolytic drugs on behavioral parameters of anxiety. In the first task we simultaneously observed behavior of adult zebrafish on four parameters: height in the tank, locomotion, color, and shoal cohesion. The second task was the assessment of light/dark preference for 5 min. The benzodiazepines clonazepam, bromazepam, diazepam, and a moderate dose of ethanol significantly reduced shoal cohesion. Buspirone specifically increased zebrafish exploration of higher portions of the tank. In the light/dark task, all benzodiazepines, buspirone, and ethanol increased time spent in the light compartment. After treatment with anxiolytics, fish typically spent more than 60s and rarely less than 40s in the light compartment whereas controls (n=45) spent 33.3±14.4s and always less than 60s in the light compartment. Propranolol had no clear effects in these tasks. These results suggest that light/dark preference in zebrafish is a practical, low-cost, and sensitive screening task for anxiolytic drugs. Height in the tank and shoal cohesion seem to be useful behavioral parameters in discriminating different classes of these drugs.

The zebrafish as a promising tool for modeling human brain disorders: A review based upon an IBNS Symposium

“…The effects of anxiolytics, antidepressants and psychostimulants on the behavior of adult zebrafish have also been investigated (see Shams and Gerlai, 2016, for a review) but opioids and cannabinoids remain understudied (Gebauer et al, 2011). For instance, exposure to anxiolytics (fluoxetine, buspirone, or diazepam) leads to impaired shoaling (Giacomini et al, 2016).…”

A Novel Method of Drug Administration to Multiple Zebrafish (<em>Danio rerio</em>) and the Quantification of Withdrawal

“…Previous studies involving drug administration in zebrafish have simply relied on netting fish to transport them from their home tank into the drug solution 12,16 . Netting is not always consistent and often takes longer than expected due to the escape response of the zebrafish, which has significant individual variability.…”

“…Previously used methods were practical, however, we sought to develop a method that reduced netting, with its associated time costs, and allowed simultaneous, precisely timed administration of the drug of interest to large numbers of fish. In traditional research using ethanol, zebrafish are netted and transferred from one tank to another containing the appropriate mixture of ethanol and water [10][11][12] . While this method is widely accepted, netting zebrafish may increase the variability in the time taken to introduce and remove the fish from the drug solution.…”

Using an Automated 3D-tracking System to Record Individual and Shoals of Adult Zebrafish

“…For instance, to explore neophobia (i.e. fear for new environments) the recording should be started immediately after introducing the zebrafish to the observation tank (after waiting just for a few seconds for the water to settle down to diminish noise), without prior habituation 11,17,37 . On the other hand, some research topics might require the zebrafish to be well habituated, for instance when studying the effects of alarm pheromones 16 .…”