Perspectives on experimental models of serotonin syndrome in zebrafish

Serotonin syndrome (SS) is a serious life-threatening disorder associated with elevated brain serotonergic function. With the growing use of serotonergic drugs, SS affects a large portion of general population, becoming a major biomedical concern. SS-like behaviors have also been reported in animals following administration of serotonergic drugs. Although clinical and rodent studies have provided significant insight into the etiology of SS, its exact mechanisms and risk factors remain poorly understood. The need to develop more efficient psychotropic drugs also requires extensive high-throughput screening of novel compounds using sensitive in-vivo tests. The use of zebrafish (Danio rerio) in neuroscience research is rapidly expanding due to their homology to humans, robust behavioral and physiological responses, genetic tractability, and low costs. Here we discuss the potential of zebrafish models to study SS-related phenotypes induced by selected serotonergic drugs. Overall, zebrafish exposed to serotonergic agents and their combinations exhibit a characteristic top dwelling (surfacing behavior) and hypolocomotion which may represent potential markers of SS-like states in zebrafish. This behavior in zebrafish models positively correlates with brain concentrations of serotonin, suggesting the developing utility of zebrafish (and other aquatic models) for studying SS. Future research is expected to foster high-throughput screening of drug interactions, and pharmacogenetics studies identifying zebrafish mutations implicated in pathological SS-like states.