Involvement of nitric oxide (NO) in the regulation of stress susceptibility and adaptation in rats

809-815The present study evaluated the regulatory role of nitric oxide (NO) in stress susceptibility and adaptation in rats. Acute restraint stress (RS ×1) reduced the number of entries and time spent in the open arms in the elevated plus maze (EPM) test and raised plasma corticosterone levels. RS (×1)-induced neurobehavioral suppression and raised corticosterone levels were attenuated by pretreatment with the NO precursor, L-arginine (500 and 1000 mg/kg)and unaffected or further aggravated by NO synthase inhibitor, L-NAME or 7-nitroindazole (10 and 50 mg/kg). Biochemical assay of plasma and brain homogenates showed that these RS – induced behavioral and neuroendocrinal changes were associated with lowered levels of plasma and brain total nitrates/nitrites (NOx). L-Arginine attenuated the RS-induced suppression of NOx levels in plasma and brain, whereas, the NO synthase inhibitors tended to produce reverse effects. In the experiments involving repeated stress i.e. RS (×5), exposure resulted in attenuation/reversal of (a) neurobehavioral suppression in the EPM test and (b) lowered brain NOx, that was seen after RS (×1). The RS (×5)-induced changes in EPM parameters and brain Nox were further potentiated after L-arginine pretreatment, whereas, the NO synthase inhibitors were less effective. Rats were screened as high and low emotional in the open-field test, and high emotional rats showed greater(a) behavioral suppression in the EPM, (b) corticosterone responses (c) brain NOx suppression, and (d) cold-restraint stress (CRS) induced gastric mucosal lesions as compared to their low emotional counterparts. L-Arginine pretreatment was more effective in modulating the above RS induced stress responses/markers in the high emotional group of rats. Our data suggest that NO plays a differential role during exposure to acute and repeated stress situations, and that the relationship between stress and emotionality status may be under the regulatory influence of NO