Age related differences in stress-induced neurobehavioral responses in rats: Modulation by antioxidants and nitrergic agents

The effect of restraint stress (RS) on neurobehavioral and brain oxidative/nitrosative stress markers and their modulation by antioxidants and nitrergic agents were evaluated in young (2 months) and old (16 months) male Wistar rats. Exposure to RS, induced anxiogenesis when tested in the elevated plus maze (EPM) and open field (OF) tests and such changes were greater in the old as compared to the young Fats. These behavioral alterations were associated with enhanced levels of malondialdehyde (MDA) and reductions in glutathione (GSH), catalase (CAT) and nitric oxide metabolites (NO,) levels in brain hornogenates-the effects being greater in intensity in the old as compared to the young animals. Pretreatment with antioxidants, alpha-tocopherol (25 and 50 mg/kg) and N-acetylcysteine (100 and 200 mg/kg) consistently reversed the RS-induced behavioral and biochemical alterations in both young and old rats. Similar attenuations of RS-induced changes were seen after pretreatment with NO precursor L-arginine (500 and 1000 mg/kg) while the NO synthase inhibitor N-nitro L-arginine methyl ester (L-NAME) (50 and 100 mg/kg) tended to aggravate the effects of RS in both age groups of rats. The results suggest that susceptibility to stress-induced neurobehavioral alterations may increase with age and interactions of reactive oxygen species (ROS) and nitric oxide in the central nervous system may exert a regulatory influence in such age dependent responses to stress. (C) 2008 Elsevier B.V. All rights reserved.