Antioxidant modulation of stress behavior depends on stress coping style: A role for N-acetylcysteine amide.

Animals experience stressors in a variety of contexts that result in activation of neuroendocrine and cellular stress responses. Release of stress hormones can disrupt or restore redox homeostasis, and the resulting changes in oxidative states, physiology and behavior vary by an individual's stress coping style. However, oxidative stress can also directly modulate neuroendocrine stress signaling. To what extent antioxidant levels alter behavioral stress levels between individuals with different stress coping styles is not well understood. The present study investigated how N-acetylcysteine amide (NACA), an antioxidant, regulates stress behavior in zebrafish (Danio rerio) with different stress coping styles (proactive, reactive). Following 24-h exposure to NACA or control conditions, we quantified individual and composite stress behaviors using a Light-Dark Test. We observed significant main effects of stress coping style and NACA-treatment on individual and composite stress behaviors where reactive fish had lower stress behaviors than proactive fish and NACA treatment reduced stress behaviors relative to controls. We observed significant stress coping style by NACA treatment interaction effects on individual and composite stress behaviors. While there was no significant reduction in stress behavior between NACA-treated and control proactive fish, NACA-treated reactive fish showed lower stress behavior than controls. Overall, our data suggest that antioxidant mechanisms (e.g., glutathione system) may be key in facilitating the distinct behavioral and physiological responses to stressors that characterize alternative stress coping styles. The results underscore how stress coping style and redox state can influence behavioral responses to stress.