Mild fructose diet during periadolescent development increases emotionality, but not metabolic consequences of early life adversity in rats

Abstract Early life stress (ELS) increases the risk of metabolic disorders such as obesity, as well as neuropsychiatric conditions including depression. Adolescence represents a critical window for metabolic programming, particularly under the influence of ELS and poor dietary habits. Animal models of ELS, such as maternal separation (MS180), induce long-term alterations in hypothalamic-pituitary-adrenal (HPA) axis function, glucose metabolism, and emotionality; however, it remains unclear whether this paradigm increases vulnerability to a chronic metabolic challenge. The aim of this study was to evaluate the effects of MS180 on male rats provided with mild fructose in drinking water starting at postnatal day (P) 21. Control and MS180 (3 h daily, from postnatal day 1 to day 14) rats were given a choice of normal water or a 10% fructose solution for 10 weeks, with standard animal facility-reared (STD) animals serving as controls. Innate emotionality was assessed using the forced swimming test. Animals were implanted with a jugular vein catheter and we evaluated fasting glucose, glucose tolerance, and baseline corticosterone (CORT) levels after one week. Our findings showed that only MS180 + Fructose rats showed a decrease in swimming and increased immobility in the forced swimming test, and previously reported effects of MS180 were only observed when performing simple comparisons. MS180 also increased body weight gain, caloric intake, impaired glucose tolerance, and elevated baseline CORT levels; however, these effects were not exacerbated by fructose. These findings suggest that even low-level fructose exposure during periadolescence may exacerbate behavioral, but not metabolic, vulnerabilities induced by ELS.