Fluoxetine ameliorates affective- and pain-related responses in adult zebrafish

Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), increases serotonin levels in the brain and modulates affective behaviors and pain. Developing reliable animal models to investigate the effects of fluoxetine across these domains is critical. The zebrafish (Danio rerio) represents a valuable vertebrate model in the field due to the well-characterized behavioral responses and conserved serotonergic system, making suitable for investigating the role of serotonin in emotion and nociception. Here, we investigated whether fluoxetine modulates behavioral phenotypes closely resembling those found in affective disorders and pain in adult zebrafish. To modulate affective domains, para-chlorophenylalanine (pCPA) was administrated for 2 consecutive days to induce increase in anxiety and depressive-like behaviors, followed by an acute fluoxetine exposure. Secondly, the protective effects of fluoxetine were tested in the acetic acid model. We found that fluoxetine reduced anxiety- and depressive-like phenotypes, as well as prevented pain-related behaviors in zebrafish. Importantly, correlations between anxiety- and despair-related phenotypes were observed, supporting the existence of distinct behavioral associations across groups. Overall, our results highlight the novelty of testing fluoxetine across multiple behavioral domains in zebrafish, reinforcing beneficial effects on affective disorders and pain response. We also reinforce the practical advantages of this aquatic species to explore the relieving properties of fluoxetine, as well as to understand the neurobiological bases involved in different behavioral phenotypes and associated therapeutic targets.