The Psychoactive Drug Escitalopram Affects Foraging Behavior in Zebrafish (Danio rerio)

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are psychoactive pharmaceuticals that have been detected intact in natural waters globally. Laboratory experiments have reported that several SSRIs inhibit fish foraging behavior, but data for the SSRI escitalopram are lacking. The objectives of the present study were to determine whether escitalopram affects feeding behavior in zebrafish and whether possible sex differences exist. We exposed female and male zebrafish (Danio rerio) to 0.00, 0.10, and 1.50 µg/L of escitalopram in flow‐through tanks for a 3‐wk exposure period. We used a video tracking system with high temporal and spatial resolution to collect data on zebrafish swimming patterns in test tanks containing a food source. The results show a more pronounced effect of escitalopram in males compared with females. At the assumed most environmentally relevant concentration (0.10 µg/L), male average feeding time/visit and maximum feeding duration were significantly reduced by 27 and 42%, respectively. In addition, male total feeding duration was also significantly reduced (by 73%) at the highest concentration (1.50 µg/L). In females, only the maximum feeding duration was significantly reduced (by 41%) in the 0.10 µg/L treatment group. Hence, we reject our initial hypothesis that female feeding behavior is more vulnerable to escitalopram. There was no effect of escitalopram on length or weight among the experimental groups. The present study demonstrates that escitalopram, like other SSRIs, can inhibit fish foraging behavior and therefore potentially disturb natural food chains. Finally, our study suggests that SSRIs can both be sex and behavior specific. Environ Toxicol Chem 2019;38:1902–1910. © 2019 SETAC.

Divergent Response to the SSRI Citalopram in Male and Female Three-Spine Sticklebacks (Gasterosteus aculeatus)

“…To our knowledge, no other study has reported such differences between males and females. Although the reason for the sex difference observed in the current study and in Nielsen et al (2019) is unknown, other effects of SSRIs, such as anxiolysis, have been shown to be sex-dependent in Endler guppy (Poecilia wingei) after exposure to citalopram (Olsén et al 2014), the Eastern mosquitofish (Gambusia holbrooki) where fluoxetine provokes a sex-divergent response in freezing behaviour (Martin et al 2017), and in rodents (Fernández-Guasti et al 2017;Lebrón-Milad et al 2013). In studies with rodents, there are mixed effects of SSRI exposure on sex difference in feeding and changes in weight (Currie et al 2004;Hutchison et al 2018).…”

“…The current study showed, for the first time, a differential response to citalopram between male and female sticklebacks and that only male sticklebacks feeding behaviour was affected by citalopram exposure. A more pronounced effect from SSRI on male feeding behaviour compared with female was previously reported in zebrafish (Danio rerio) (Nielsen et al 2019). Nielsen et al (2019) used escitalopram, the active S-enantiomere of citalopram.…”

“…A more pronounced effect from SSRI on male feeding behaviour compared with female was previously reported in zebrafish (Danio rerio) (Nielsen et al 2019). Nielsen et al (2019) used escitalopram, the active S-enantiomere of citalopram. To our knowledge, no other study has reported such differences between males and females.…”

Zebrafish as an Animal Model for Testing Agents with Antidepressant Potential

“…They found out that adult female zebrafish are more sensitive to the effects of fluoxetine when exposed to the drug between the 15th and the 42nd dpf (i.e., during the period of late sexual development)—they presented a considerable level of the exploratory behavior, whereas adult male zebrafish are more sensitive to the effects of fluoxetine when exposed to the drug during the period of early sexual development (i.e., up to the 15th dpf)—they displayed reduced activity. The results obtained by Nielsen et al [ 130 ] also suggest that selective serotonin reuptake inhibitors may induce the sex-specific swimming behaviors in zebrafish. According to the literature data [ 124 , 131 ], a sex-dependent behavioral response in zebrafish can be associated with the sex-dependent levels of androgens and estrogens as well as with the sex-dependent differences in serotonin production.…”

Factors Determining the Susceptibility of Fish to Effects of Human Pharmaceuticals

“…Examples include disruptions in anxiety-and aggression-related behaviors in zebrafish (Danio rerio) and Siamese fighting fish (Betta splendens) exposed to fluoxetine 40,41 and suppressed foraging behavior in zebrafish exposed to escitalopram. 42 Although evidence exists that some human pharmaceuticals can affect the physiological functioning and/or behavior of individual fish, very little is known about their impact at population level. Indirect impacts of APIs on fish via their effects on other trophic groups, and vice versa, have been indicated, 28 but this is not the focus of this review.…”