Zebrafish as a potential non-traditional model organism in translational bipolar disorder research: Genetic and behavioral insights

Bipolar disorder (BD) is a severe and debilitating illness that affects 1–2% of the population worldwide. BD is characterized by recurrent and extreme mood swings, including mania/hypomania and depression. Animal experimental models have been used to elucidate the mechanisms underlying BD and different strategies have been proposed to assess BD-like symptoms. The zebrafish (Danio rerio) has been considered a suitable vertebrate system for modeling BD-like responses, due to the genetic tractability, molecular/physiological conservation, and well-characterized behavioral responses. In this review, we discuss how zebrafish-based models can be successfully used to understand molecular, biochemical, and behavioral alterations paralleling those found in BD. We also outline some advantages and limitations of this aquatic species to examine BD-like phenotypes in translational neurobehavioral research. Overall, we reinforce the use of zebrafish as a promising tool to investigate the neural basis associated with BD-like behaviors, which may foster the discovery of novel pharmacological therapies.