Modulation of Caffeine-Induced Behavioral Alterations by N-Acetylcysteine in a Pharmacological Challenge Model.

Background

Caffeine is a widely consumed psychostimulant that may affect anxiety-like, aggression-like, and social behaviors, potentially in association with oxidative imbalance.

Objectives

This study evaluated the behavioral and biochemical effects of acute caffeine exposure in adult zebrafish and investigated the potential protective effects of N-acetylcysteine (NAC).

Methods

Sixty adult wild-type AB zebrafish (Danio rerio), approximately 9-10 months old, were assigned to six groups (n = 10/group): control, caffeine (25 or 60 mg/L), NAC (1 mg/L), and NAC combined with either caffeine concentration. Behavioral effects were assessed using the Social Preference Test, Mirror-Biting Test, and Novel Tank Test. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured as oxidative stress-related markers.

Results

Caffeine increased locomotor activity and induced anxiety-like and aggression-like behavioral alterations, including increased bottom-dwelling, thigmotaxis, and mirror-directed behavior, while reducing social preference. Caffeine significantly increased SOD activity at 25 mg/L (p = 0.010) and 60 mg/L (p = 0.008), and GPx activity at 25 mg/L (p = 0.008) and 60 mg/L (p = 0.006), compared with controls. NAC attenuated caffeine-induced hyperlocomotion and several anxiety-like and aggression-like alterations and modulated antioxidant enzyme responses, but did not fully restore social preference.

Conclusions

Acute caffeine exposure produces behavioral alterations and changes in antioxidant enzyme activity in adult zebrafish. NAC partially attenuates these effects, particularly hyperlocomotion, anxiety-like behavior, and aggression-like responses, while showing more limited effects on caffeine-induced social alterations.