Zebrafish (Danio rerio) as a model to assess the effects of cocaine as a drug of abuse and its environmental implications.

Cocaine (COC) use concerns are on the increase for both authorities and civil society. Despite this, it is important to investigate COC effects or those of its main metabolite, belzoylecgonine (BE), in consolidated aquatic model organisms, such as the zebrafish (Danio rerio). This (mini) review consists in an assessment regarding toxicological studies carried out employing zebrafish (embryos, larvae or adults) exposed to COC and/or BE indexed at the SCOPUS and Web of Science databases. Ten different endpoints were analyzed in both embryos and larvae, whereas only four were analyzed in adults. Of the 23 studies, only five investigated COC and/or BE effects following an environmental approach when exposing zebrafish, while most (18 studies) analyzed COC effects under a drug of abuse approach. Cocaine exposure was noted as altering the expression of several genes, such as those linked to COC transport proteins, dopamine receptors, SP substance production, the tachykinin system, and the tyrosine hydroxylase enzyme. BE exposure resulted in more oxidative and proteomic effects than COC in embryos. Cocaine abstinence resulted in hyperactivity associated with stereotypy in adult fish, in addition to reduced responses to visual stimuli to red light and neuronal development pattern alterations. Cocaine was noted as accumulating in zebrafish eyes, possibly due to melanin binding, and causing dose-response cardiac effects in both embryos and adults. Despite the different effects addressed by our survey, we emphasize the lack of COC and BE exposure assessments in zebrafish employing an environmental point of view.