Purpose: Stress activates the sympathetic nervous system and hypothalamic–pituitary–adrenal (HPA) axis and induces the release of glucocorticoids. Saccharin is 300 times sweeter than sucrose, but does not increase blood insulin levels. Thus, this study was designed to evaluate the effect of saccharin intake in restraint-induced stress response reduction in rats. Methods: Adult male Sprague-Dawley (SD) rats had stress induced by restraint for 2 hours/day for 1 week. Saccharin was provided in sufficient amounts to allow them to intake it voluntarily at 0.1% diluted in water. The Y-maze test and forced swim test (FST) were performed to evaluate cognitive function and the depressive behavior of the rats. The protein expression of the glucocorticoid receptor (GR) in hippocampal cornu ammonis (CA) 1 was investigated by using immunohistochemistry. Results: It was found that, the percentage of alternation in the Y-maze test was significantly (p<.01) higher in the Stress + saccharin group than in the Stress group. Immobility time in the FST was significantly (p<.01) lower in the Stress + saccharin group than in the Stress group. Also, the positive cells of GR in hippocampus CA1 were significantly (p<.05) lower in the Stress + saccharin group than in the Stress group. Conclusion: This study showed that there was an effect of saccharin intake in restraint-induced stress response reduction in rats.
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