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.

Highlights

  • Alcohol is amongst the most commonly abused legal substances worldwide (World Health Organization, 2011)

  • Repeated ethanol exposure: time in zones In order to quantify the impact of ethanol-induced withdrawal on anxiety and exploratory behaviour, the time spent in the centre, transition, and thigmotaxis zones of the arena were quantified

  • We did not observe a significant difference in time spent in each of the transition (Fig. 2B; control: 204.4 ± 29.6 s, n = 18; 0.4%: 216.2 ± 31.4 s, n = 16; 0.8%: 174.6 ± 41.0 s, n = 17; H(3, 51) = 2.803, P = 0.2462), or thigmotaxis (Fig. 2C; control: 685.7 ± 30.8 s, n = 18; 0.4%: 672.9 ± 32.5 s, n = 16; 0.8%: 722.5 ± 40.9 s, n = 17; H(3, 51) = 3.217, P = 0.2002) zones following ethanol exposure, at either 0.4% or 0.8% ethanol exposure conditions compared to controls

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Summary

Introduction

Alcohol (ethanol) is amongst the most commonly abused legal substances worldwide (World Health Organization, 2011). Excessive and repeated alcohol use is known to cause significant impairments in behaviour and physiology. Many of the detriments of alcohol use come from repeated exposure due to an addiction called alcohol use disorder (Levinthal & Hamilton, 2015; American Psychiatric Association, 2013). Alcohol use disorder can be characterized by several symptoms: an impulse to seek out and consume alcohol, inhibition of controlled consumption, and the emergence of a negative emotional state during withdrawal (Vendruscolo & Roberts, 2014), as well as many negative physical manifestations leading to increased mortality (Kendler et al, 2016). Along with the severe health and behavioural detriments, alcohol abuse is a societal and economic burden that is undertreated (Holt & Tobin, 2018). The difficulty lies in the fact that individuals addicted to alcohol consumption that refrain from alcohol use will often

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