Abstract
Zebrafish (Danio rerio) have emerged as a popular model for studying the pharmacology and behavior of anxiety. While there have been numerous studies documenting the anxiolytic and anxiogenic effects of common drugs in zebrafish, many do not report or test for behavioral differences between the sexes. Previous studies have indicated that males and females differ in their baseline level of anxiety. In this study, we test for a sex interaction with fluoxetine and nicotine. We exposed fish to system water (control), 10 mg/L fluoxetine, or 1 mg/L nicotine for three minutes prior to being subjected to four minutes in an open-field drop test. Video recordings were tracked using ProAnalyst. Fish from both drug treatments reduced swimming speed, increased vertical position, and increased use of the top half of the open field when compared with the control, though fluoxetine had a larger effect on depth related behaviors while nicotine mostly affected swimming speed. A significant sex effect was observed where females swam at a slower and more constant speed than males, however neither drug produced a sex-dependent response.
Highlights
The zebrafish (Danio rerio) is a popular research model for studying pharmacology and behavior (Gerlai, 2015), with regard to stress and anxiety
Exposure to anxiolytic drugs alters these behaviors in ways that may indicate an association between anxiety related behaviors and risk management
We observed a decrease in bottom dwelling and an increase in time spent in the top half of the tank in fish exposed to fluoxetine (Figs. 3 and 4)
Summary
The zebrafish (Danio rerio) is a popular research model for studying pharmacology (summarized in Barros et al, 2008; Langheinrich, 2003) and behavior (Gerlai, 2015), with regard to stress and anxiety. Sex-specific differences were observed in the effectiveness of the SSRI Fluoxetine in humans (Martényi et al, 2001), and studies utilizing rats (Mitic et al, 2013; Leuner, Mendolia-Loffredo & Shors, 2004; Lifschytz et al, 2006) and mice (Monleón et al, 2002; Hodes et al, 2010) have shown a discrepancy between the sexes in both the physiological and behavioral responses to this drug where efficacy tends to be greater in females than in males. These substances were chosen because they have known anxiolytic effects across a wide variety of model systems including humans (Gilbert, 1979; Griffin & Mellon, 1999), rats (Cohen et al, 2009; Zhang et al, 2000) and zebrafish (Bencan & Levin, 2008; Bencan, Sledge & Levin, 2009; Cachat et al, 2010; Levin, Bencan & Cerutti, 2007), and while sex-specific effects have been observed in mammals, studies in zebrafish utilizing these substances largely ignore the effects of sex
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