Pharmacological and Toxicological Effects of Lithiumin Zebrafish

摘要

Lithium is the paradigmatic treatment for bipolar disorder and has been widely used as a mood stabilizer due to its ability to reduce manic 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. However, they are credited at least partially to 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 in different systems and developmental stages. 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 suitable model. In addition, zebrafish has been establishedas an effective model organism in behavioral and neuropharmacologicalstudies, reacting to a wide range of psychoactive drugs, includinglithium. So far only a limited number of studies evaluated the toxicologicalimpact of lithium on zebrafish development and demonstrated morphological,physiological, and behavioral effects that may be informative regardinghuman findings. Further studies dedicated to characterize and evaluatethe underlying mechanisms of the toxic effects and the potential impactof exposure on developing and adult individuals are necessary to establishsafe clinical management guidelines for women with bipolar disorderof childbearing age and safety disposal guidelines for pharmaceuticalneuroactive compounds.