There is accumulating evidence on the use of N-acetylcysteine (NAC) in the treatment of patients with neuropsychiatric disorders. As a multi-target drug and a glutathione precursor, NAC is a promising molecule in the management of stress-related disorders, for which there is an expanding field of research investigating novel therapies targeting oxidative pathways. The deleterious effects of chronic stress in the central nervous system are a result of glutamatergic hyperactivation, glutathione (GSH) depletion, oxidative stress, and increased inflammatory response, among others. The aim of this study was to investigate the effects of NAC in zebrafish submitted to unpredictable chronic stress (UCS). Animals were initially stressed or not for 7 days, followed by treatment with NAC (1 mg/L, 10 min) or vehicle for 7 days. UCS decreased the number of entries and time spent in the top area in the novel tank test, which indicate increased anxiety levels. It also increased reactive oxygen species (ROS) levels and lipid peroxidation (TBARS) while decreased non-protein thiols (NPSH) and superoxide dismutase (SOD) activity. NAC reversed the anxiety-like behavior and oxidative damage observed in stressed animals. Additional studies are needed to investigate the effects of this agent on glutamatergic modulation and inflammatory markers related to stress. Nevertheless, our study adds to the existing body of evidence supporting the clinical evaluation of NAC in mood disorders, anxiety, post-traumatic stress disorder, and other conditions associated with stress.

Alcohol hangover refers to unpleasant symptoms experienced as a direct consequence of a binge drinking episode. The effects observed in this condition are related to the increase in alcohol metabolites and imbalance in oxidative status. N-acetylcysteine (NAC) is a mucolytic agent and an antidote for paracetamol overdose. Preclinical and clinical studies have shown that NAC is a multi-target drug acting through neuroprotective, antioxidant and neurotrophic mechanisms as well as a glutamate modulator. The aim of this study was to investigate the effects of NAC in zebrafish acutely exposed to ethanol (EtOH). Animals pretreated or not with NAC (1 mg/L, 10 min) were exposed for 60 min to standard tank water (EtOH-) or to 1% EtOH (EtOH+) to evaluate anxiety-like behavior and locomotion in the novel tank test and oxidative damage in the brain. Zebrafish (Danio rerio) exposed to EtOH displayed a decrease in the distance traveled, crossings, entries and time spent in the top area in the novel tank test. Exposure to EtOH also caused oxidative damage, shown by increased lipid peroxidation, decreased non-protein thiols and increased production of reactive oxygen species (DCF assay). NAC prevented both the behavioral alterations and the oxidative stress observed in EtOH+ animals. Given the effects of NAC in preventing the acute behavioral and biochemical effects of EtOH, additional studies are warranted to further investigate the basis of its anecdotal use to prevent hangover.