Pharmacological and Toxicological effects of lithium in zebrafish

Lithium is the paradigmatic treatment for bipolar disorder and has been widely used as a mood due to its ability to reduce maniac and depressive episodes, efficiency in long-term mood stabilization and effectiveness in reducing suicide risks. Despite many decades of clinical use, the molecular targets of lithium are not completely understood but attributed to and glycogen synthase kinase 3 (GSK3) inhibition mimicking and exacerbating Wnt signaling pathway activation. There has been a great effort to characterize lithium cellular and system actions, aiming to improve treatment effectiveness and reduce side effects. There is also a growing concern about lithium's impact as an environmental contaminant and its effects on development. In this scenario, zebrafish is a helpful model organism to gather more information on lithium's effects. The rapid external development, initial transparency, capacity to easily absorb substances and little space required for maintenance and experimentation, among other advantages, make zebrafish a great animal model for study drug effects. In addition, zebrafish has been established as an effective model organism in behavior and neuropharmacology studies, reacting to a wide range of psychoactive drugs, including lithium. So far only a limited number of studies evaluated the toxicological impact of lithium on zebrafish development and demonstrate morphological, physiological and behavioral deleterious effects. Further studies dedicated to characterize and evaluate the underlying mechanisms of the toxic effects and the potential impact of exposure on developing and adult individuals are necessary to establish safe clinical management guidelines for woman with bipolar disorder of childbearing age and safety disposal guidelines for pharmaceutical neuroactive compounds.