Effect of diet and sex on changes in gene expression and behavioral responses to chronic stress

This work investigated the interaction between sex, stress, and dietary choice in rats. A preferred diet under the influence of chronic mild stress (CMS) was empirically determined to consist of soybeans and cookies mixed with lab chow. This mixed preferred diet was tested for its ability to mitigate the behavioral effects of CMS. Changes in the expression of genes selected for their known involvement in neurotrophic processes, response to stress, and appetite regulation were also studied in relation to these three factors. Stressed rats of both sexes decreased their frequency of rearing and increased their attention to novelty. In the elevated plus maze, unstressed males but not females spent more time in the closed arm, even if fed the preferred diet. By stressing the animals, the comforting consequences of the preferred diet appeared to be overshadowed. In the forced swim test, females but not males fed the preferred diet showed increased immobility, whether stressed or not. Finally, females but not males showed a differential effect of diet under stress on the sucrose preference test. Only for the stressed females was the preferred diet effective in promoting sucrose intake, suggesting that the preferred diet did serve as a comfort food in this case. These results suggest that male and female rats differ in their susceptibility to the behavioral-modifying influences of CMS. And, to the extent that diet serves as a coping mechanism, it does so differently in males and females. Differential results were reported in gene data that may well be explained by differences in the nature and duration of the chronic stress employed. In many cases, the gene expression changes found in our study showed regional differences between the hypothalamus and amygdala in their sensitivity to stress and diet. This suggests that different stressors activate different areas of the brain, and that distinct afferent pathways mediate responses specific to the nature of the stress. The most important conclusion of this study is that gene expression responses to stress depend on sex, diet, and brain region, in a pattern unique for each gene