Roles of the 5-HT2C receptor on zebrafish sociality

Abstract

Serotonin (5-HT) receptors have been implicated in social behavior in vertebrates. Zebrafish (Danio rerio) have been increasingly being used behavioral neuroscience to study the neurobiological correlates of behavior, including sociality. Nonetheless, the role of 5-HT2C receptors in different social functions were not yet studied in this species. Zebrafish were treated with the agonist MK-212 (2 mg/kg) or the antagonist RS-102221 (2 mg/kg) and tested in the social interaction and social novelty tests, conditional approach test, or mirror-induced aggressive displays. MK-212 increased preference for an unknown conspecific in the social investigation test, but also increased preference for the known conspecific in the social novelty test; RS-102221, on the other hand, decreased preference in the social investigation test but increased preference for the novel conspecific in the social novelty test. MK-212 also decreased predator inspection in the conditional approach test. While RS-102221 decreased time in the display zone in the mirror-induced aggressive display test, it increased display duration. Overall, these results demonstrate the complex role of 5-HT2C receptors in different social contexts in zebrafish, revealing a participation in social plasticity in vertebrates.

Roles of the 5-HT1A receptor in zebrafish responses to potential threat and in sociality

“…While social approach is sensitive to acute stress in adult zebrafish (Cook et al, 2023), the fact that, differently from lab rodents, zebrafish do not avoid novel conspecifics, and actively spend time investigating them when possible (Barba-Escobedo & Gould, 2012;do Nascimento & Maximino, 2023;Ogi et al, 2021), makes it difficult to understand how threat factors in sociability in this species. The activation of 5-HT2 receptors has been shown to increase sociability in zebrafish (de Moura et al, 2023;Ponzoni et al, 2016), and singlenucleotide polymorphisms of the htr1aa gene (which code for one isoform of the 5-HT1A receptor) mediate populational variability in social exploration and sociability in this species (Gonçalves et al, 2022). These results further underscore the role of serotonin in sociability in zebrafish, with opponent modulation by 5-HT1AR and 5-HT2CR agonists.…”