Female adult zebrafish (Danio rerio) show higher levels of anxiety‐like behavior than males, but do not differ in learning and memory capacity

Abstract

Zebrafish (Danio rerio) are widely used as a translational model for human neuropsychiatric conditions. Many studies have not considered sex differences in their analyses. Here, we studied sex differences of adult zebrafish in two behavioral domains: Anxiety and Memory. To assess whether sex influences anxiety-like responses, we used two different behavioral protocols, the novel tank diving task and the light-dark test. To assess sex differences in learning and memory tasks, we explored two memory domains, short-term spatial memory (free movement pattern Y-maze task) and short-term fear memory (Pavlovian fear conditioning task). Although we did not find any significant difference in learning and memory tasks, female zebrafish showed robust increases in anxiety-like behavioral endpoints in both anxiety tests. Overall, our data suggest that zebrafish is a sensitive model to work with sex differences when modeling anxiety-related disorders and this should be an important factor to consider in different experimental designs.

A Test of Memory: The Fish, The Mouse, The Fly And The Human

“…A total of N=166 zebrafish (Danio rerio) of AB wild-type strain (4 months-old at time of testing) male and female (~50:50) were bred in house and raised in the University of Portsmouth Fish Facility. Previous work from our lab has revealed no differences in search strategy between male and female zebrafish 27 . Fish were assigned at random to each treatment group from >10 groups of n = 11-18 fish per 2.8L tanks on a re-circulating system (Aquaneering Inc., San Diego, CA, USA).…”

“…Procedure FMP Y-maze exploration task. The protocol was carried out as described in our previous papers 27,28,33 . Briefly, animal handling and experimenter visibility were both kept to a minimum.…”

Zebrafish models of impulsivity and impulse control disorders

“…Sex is another biological variable that can strongly influence zebrafish ICD‐related traits, such as aggressive behavior and locomotor activity. However, further studies are needed to investigate whether impulsivity and other ICD‐like traits are differentially expressed in male vs. female fish (Ariyomo & Watt, 2013; Dahlbom et al., 2012; Fontana et al, 2019; Genario et al., 2019), similar to the well‐established sex differences in humans (Demmer et al., 2017; Maughan et al., 2004).…”

“…Impulsive behaviors are also associated with sex‐specific ICD‐like traits that can also be targeted in zebrafish (Genario, de Abreu, Giacomini, Demin, & Kalueff, 2019). For example, female zebrafish are more active and anxious than males (Fontana, Cleal, & Parker, 2019; Genario et al., 2020), whereas both sexes show similar levels of baseline aggressive behaviors (Ariyomo, Carter, & Watt, 2013; Dahlbom, Backström, Lundstedt‐Enkel, & Winberg, 2012) (Figure 3). However, when challenged, zebrafish may reveal sex differences in aggression.…”

“…Selected advantages of zebrafish as a model organism of impulsivity and impulse control disorders (ICD) include the presence of impulsivity models in both larvae and adult fish (Parker, Ife, et al, 2013), share approximately 67% homology for “aggressive” genes with humans (de Abreu, et al., 2019), display sex differences in ICD‐related traits (e.g., female zebrafish are more active and anxious than males (Fontana et al, 2019; Genario et al., 2020)) and utilize cortisol in stress response like humans, but unlike in rodents, that use corticosterone (Demin et al., 2020). 5‐CSRTT, a continuous performance test used to assess impulsivity and attention…”