Efeitos neuroendócrinos e comportamentais do aripiprazol em zebrafish

Abstract

The aripiprazole (APPZ) is a second-generation atypical antipsychotic, which has been increasingly used in the treatment of psychoses, such as schizophrenia, autism, bipolar affective disorder, among others. The increasing use of this drug occurs because it causes less extrapyramidal effects compared to typical antipsychotics. Associated with the increase in prescriptions and, consequently, in the consumption of this drug, there is, consequently, a growing risk of environmental contamination by its residues, either in active form or in the form of metabolites. These residues in the environment can affect non-target organisms such as fish, interfering negatively in their homeostasis and in their physiological defense mechanisms. Several studies have demonstrated the problematic of the contamination of aquatic environments and the impact on the fauna of these ecosystems by several psychotropic drugs. In this context, the aim of the present study was to verify if aripiprazole changes the endocrine and behavioral responses to stress in adult zebrafish. We have shown, based on the results described in the two articles presented, that APPZ residues in water produce effects on both the hypothalamic-pituitary-interrenal (HHI) axis and in the behavior of adult zebrafish. In the first article, we show that the fish previously exposed to APPZ, when subjected to the acute stressor, presented a blunted cortisol response to stress. Regarding to the effect of APPZ on zebrafish behavior, we observed that some of the tested concentrations reversed the behavioral response to stress in both the social preference, the anxiety-like behavior and the perception of a stimulus fish, whether predator or not predator. Thus, we conclude that acute exposure to APPZ is capable of blunting the neuroendocrine axis of stress in adult zebrafish, as well as altering exploratory and social behavior and reaction to a predatory threat. In an ecological context, the sum of these endocrine and behavioral effects caused by APPZ may expose fish to a greater risk of predation and, consequently, increase the risk of broken of ecological balance between species, and consequently impact the aquatic ecosystem.