Neuropsychiatric disorders often derive from environmental influences that occur at important stages of development and interact with genetics. This study examined the effects of stress during adolescence in rats selectively bred for different behavioral responses to stress. The effects of chronic adolescent stress were compared between rats selected for susceptibility to reduced activity following acute stress (Swim-test Susceptible rats) and rats resistant to activity reduction after acute stress (Swim-test Resistant rats). Consistent with lineage, exposure to chronic adolescent stress increased swim-test activity of the Swim-test Resistant rats while tending to reduce activity of the Swim-test Susceptible rats. Consistent with the increased activity demonstrated post-stress in the swim test, chronic adolescent stress increased total activity in the open field for Swim-test Resistant rats. Indicative of anhedonia, chronic adolescent stress exposure decreased sucrose consumption in both male and female Swim-test Resistant rats but only in female Swim-test Susceptible rats. Although chronic stress induced changes in behavior across both breeding lines, the precise manifestation of the behavioral change was dependent on both breeding line and sex. Collectively, these data indicate that selective breeding interacts with chronic stress exposure during adolescence to dictate behavioral outcomes.

Fructose consumption, which promotes insulin resistance, hypertension, and dyslipidemia, has increased by over 25% since the 1970s. In addition to metabolic dysregulation, fructose ingestion stimulates the hypothalamic-pituitary-adrenal (HPA) axis leading to elevations in glucocorticoids. Adolescents are the greatest consumers of fructose, and adolescence is a critical period for maturation of the HPA axis. Repeated consumption of high levels of fructose during adolescence has the potential to promote long-term dysregulation of the stress response. Therefore, we determined the extent to which consumption of a diet high in fructose affected behavior, serum corticosterone, and hypothalamic gene expression using a whole-transcriptomics approach. In addition, we examined the potential of a high-fructose diet to interact with exposure to chronic adolescent stress. Male Wistar rats fed the periadolescent high-fructose diet showed increased anxiety-like behavior in the elevated plus maze and depressive-like behavior in the forced swim test in adulthood, irrespective of stress history. Periadolescent fructose-fed rats also exhibited elevated basal corticosterone concentrations relative to their chow-fed peers. These behavioral and hormonal responses to the high-fructose diet did not occur in rats fed fructose during adulthood only. Finally, rats fed the high-fructose diet throughout development underwent marked hypothalamic transcript expression remodeling, with 966 genes (5.6%) significantly altered and a pronounced enrichment of significantly altered transcripts in several pathways relating to regulation of the HPA axis. Collectively, the data presented herein indicate that diet, specifically one high in fructose, has the potential to alter behavior, HPA axis function, and the hypothalamic transcriptome in male rats.