Investigação do mecanismo de ação da N-acetil cisteína em um modelo de estresse crônico imprevisível em peixes-zebra

Abstract

Mental disorders are highly prevalent in society, producing deleterious effects on individuals and healthcare systems. Despite this, treatments with greater efficacy and adherence, as well as lower rates of adverse effects, are lacking, reinforcing the need for new therapies. In this context, N-acetylcysteine (NAC) emerges as a promising drug for the treatment of mental disorders, mainly due to its neuroprotective capacity. In this sense, the study evaluated the sustained anxiolytic-like effect of NAC after a single exposure in zebrafish subjected to the Chronic Unpredictable Stress (CUS) protocol. After habituation, the animals were initially divided into a stressed group (4 groups) and a non-stressed group (4 groups). After 7 days of CUS, the animals were subdivided according to treatment exposure into control (system water), NAC (10 mg/L), ketamine (20 mg/L), or fluoxetine (10 mg/L), with each of these containing a non-stressed group and a stressed group. The fish were exposed on day 7 to one of the treatments for 20 minutes and immediately returned to their home tank. 24 hours after drug exposure, the animals were subjected to the novel tank test and filmed for 6 minutes. A two way ANOVA test, followed by Tukey's post hoc test, was used for the analysis of the interventions. The significance level adopted was p<0.05. As expected, CUS reduced the number of crossings and the time spent in the upper area, and increased the time spent in the lower area, conferring an anxiogenic-like behavior. NAC and KET attenuated the anxiogenic like effect induced by CUS in a sustained manner after a single exposure to the treatment. Furthermore, FLU showed an anxiolytic-like behavior in non-stressed animals. Here, we demonstrate for the first time the sustained effect of NAC in attenuating the anxiogenic-like effects induced by CUS in zebrafish after a single therapeutic intervention for 20 minutes. Given the positive effect of NAC, its good safety profile, and low cost, it emerges in the treatment or as an adjuvant for stress-related neuropsychiatric disorders. More studies are needed to better evidence the effects of NAC, as well as to establish the mechanism of action.