The dopamine transporter inhibition using GBR 12909 as a novel pharmacological tool to assess bipolar disorder-like neurobehavioral phenotypes in zebrafish.

Dopamine (DA) is a neurotransmitter that plays an important role in brain physiology. Changes in DA-mediated signaling have been implicated with the pathophysiology of various neuropsychiatric conditions. Bipolar disorder (BD) is a mental disorder, characterized by alterning between manic/hypomanic and depressive mood. In experimental research, the pharmacological inhibition of DA reuptake using GBR 12909 serves as a tool to elicit BD-like phenotypes. Alternative model organisms, such as the zebrafish (Danio rerio), have been considered important systems for investigating the neurobehavioral changes involved in different neuropsychiatric conditions, including BD. Here, we discuss the use of GBR 12909 as a novel pharmacological strategy to mimic BD-like phenotypes in zebrafish models. We also emphasize the well-conserved DA-mediated signaling in zebrafish and the early expression of dopaminergic biomarkers in the brain, especially focusing on dopamine transporter (DAT), the main target of GBR 12909. Finally, we discuss potential advantages and limitations in the field, the perspectives of using GBR 12909 in BD research, and how distinct validation criteria (i.e., face, predictive, and construct validity) can be assessed in translational approaches using zebrafish-based models.