Effects of chronic stress are not completely understood. They may underlie 
depression and dementia. This study assessed the association between chronic 
stress, glutamate levels, tau-protein phosphorylation, and nitric-oxide in old 
rats exposed to chronic mild stress (CMS). Old (>15 months) male Wistar rats 
were exposed to CMS. Comparison groups included old and young control rats, 
young CMS-exposed, and old CMS-exposed rats treated with the neuronal 
nitric-oxide synthase (nNOS) enzyme inhibitor, 7-nitroindazole (20 mg/kg/day 
i.p.). Hippocampal glutamate levels and glutamate decarboxylase (GAD) activity 
were determined and tau protein phosphorylation was assessed. Age was a 
significant (p=0.025) source of variation in glutamate level [811.71+/-218.1, 
665.9+/-124.9 micromol/g tissue protein (M+/-SD) in young and old control rats, 
respectively]. Old rats exposed to CMS were characterized by an increased risk 
to develop anhedonia. There was significant (p=0.035) decrease in GAD enzyme 
activity (-60.06%) and increased tau protein hyperphosphorylation in old rats 
exposed to CMS compared to control. Administration of 7-nitroindazole to 
CMS-exposed old rats significantly (p=0.002) increased GAD activity, decreased 
glutamate levels (7.19+/-3.19 vs. 763.9+/-91 micromol/g tissue protein; 
p=0.0005), and decreased phosphorylation of tau proteins compared to CMS exposed 
rats.