The effect of restraint stress (RS) on neurobehavioral and brain oxidative stress parameters, and their modulation by antioxidants were evaluated in male and cycling female rats. Exposure to RS suppressed both open arm entries and open arm time in the elevated plus maze and these changes were more marked in males than in females. Assay of brain homogenates revealed that the behavioral suppression was associated with similar differential increases in malondialdehye (MDA) and decreases in glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels in males and females. Pretreatment with α-tocopherol (25 and 50 mg/kg) and N-acetylcysteine (100 and 200 mg/kg), attenuated the stress induced alteration of behavioral and oxidative stress markers in a consistent manner in both male and female rats. These findings suggest that males may be more susceptible than females to stress induced neurobehavioral changes and free radicals may exert a regulatory influence in such gender dependent responses to stress. © 2007 Elsevier B.V. All rights reserved.