Pharmacological and biochemical studies on the possible role of nitric oxide in stress adaptation in rats

The involvement of nitric oxide (NO) in stress adaptation was evaluated in rats using the elevated plus maze test. Repeated restraint stress RS(×5) for 5 days resulted in an increase in the percentage number of entries and percentage time spent when compared to a single restraint stress RS(×1) exposure. In the repeated RS treatment groups, the nitric oxide donor, l-arginine (500 and 1000 mg/kg, i.p.) slightly increased the elevated plus maze test parameters when compared to the corresponding vehicle-treated group. The nitric oxide synthase (NOS) inhibitors, N-nitro- l-arginine methyl ester ( l-NAME, 10 and 50 mg/kg, i.p.) and 7-nitroindazole (10 and 50 mg/kg, i.p.) produced differential responses in both the parameters with l-NAME exhibiting greater reduction in open arm entries and open arm time, whereas 7-nitroindazole produced only small differences in both the elevated plus maze parameters. Biochemical data showed that repeated restraint stress resulted in higher levels of brain nitrates and nitrites (NO x) as compared to that of single restraint stress exposure. Further, in l-arginine (1000 mg/kg, i.p.)-treated rats, brain NO x was lowest in the single restraint stress group, followed by repeated restraint stress and (no restraint stress) controls. The results are suggestive of the role of nitric oxide in stress adaptation and this may be due to the effects of restraint stress on brain NOS activity.