Repeated ethanol exposure increases anxiety-like behaviour in zebrafish during withdrawal

Abstract

Zebrafish (Danio rerio) are quickly becoming an important model organism in behavioural neuroscience and drug addiction research. Conditioned place preference studies show that drugs of abuse produce responses in zebrafish that are similar to mammalian animal models. Repeated administration of ethanol in zebrafish results in withdrawal-induced behavioural responses that vary with dose and exposure duration, requiring additional investigation. Here, we examine the effects of ethanol withdrawal on anxiety-like behaviours in adult zebrafish after a 21-day ethanol dosing schedule at either 0.4% or 0.8%. Anxiety-like behaviour was measured with the novel object approach test; this test involves placing a fish in a circular arena with a novel object in the centre and observing the amount of exploration of the object. We found increased anxiety-like behaviour during ethanol withdrawal. This study adds to the growing body of literature that validates the zebrafish as a model organism in the field of behavioural neuroscience and addiction.

Opposing effects of acute and repeated nicotine exposure on boldness in zebrafish

“…3B). Notably, we administered the novel object approach test immediately after dosing, consistent with other research using this test [34][35][36][37] , however, the peak effects of nicotine with 3-minutes of exposure may be not be observed until 20-40 minutes later 18 .…”

“…Pharmacological compounds that normally alter anxiety, such as caffeine 33 and the GABA A -receptor antagonist, gabazine 34 have been studied with the novel object approach test and both increased the time fish spent in the thigmotaxis zone. Conversely, anxiolytic drugs like ethanol increase the time spent in the transition zone near the novel object 35,36 . Therefore, increased www.nature.com/scientificreports www.nature.com/scientificreports/ object exploration (more time spent in transition or inner zones and less time in the thigmotaxis zone) are likely to be indicative of reduced anxiety in zebrafish.…”

“…A Lego figurine (2 cm × 4.25 cm; Fig. 1D) which was multi-coloured and identical to previous studies [34][35][36][37] was used to rule out any possible colour (2020) 10:8570 | https://doi.org/10.1038/s41598-020-65382-6 www.nature.com/scientificreports www.nature.com/scientificreports/ preferences 51 . This novel object was positioned in the center of the arena.…”

Behavioral effects of developmental exposure to JWH-018 in wild type and disrupted in schizophrenia 1 (disc1) mutant zebrafish

“…When anxiety-like behavior was assessed during adulthood, we observed wild-type zebrafish developmentally exposed to JWH-018 spent less time on the bottom of the tank, suggesting they were less anxious when placed in a new environment compared to non-exposed animals. These results challenge previous reports suggesting anxiogenic effects due to drug withdrawal in zebrafish [46,47]. However, none of these studies exposed fish to JWH-018, nor they exposed them at early developmental stages and tested months after withdrawal, limiting their comparability.…”

Vision of conspecifics decreases the effectiveness of ethanol on zebrafish behaviour

“…To explore this, we exposed individual zebrafish to either habitat water or ethanol (1.0% vol/vol) while untreated conspecifics were visually present or absent for the entire exposure period. Following exposure, the treated fish were transferred to the novel object approach test for quantification of anxiety-like behaviour and boldness ( Dean et al, 2020 ; Krook et al, 2019 ; Leighton et al, 2018 ). Finally, we tested whether fish move at different rates and remain closer to conspecifics during the dosing period itself in order to determine whether the social condition ( Isolated vs. In-view ) influences behaviour during drug exposure.…”