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.

The developmental period constitutes a critical window of sensitivity to stress. Indeed, early-life adversity increases the risk to develop psychiatric diseases, but also gastrointestinal disorders such as the irritable bowel syndrome at adulthood. In the past decade, there has been huge interest in the gut–brain axis, especially as regards stress-related emotional behaviours. Animal models of early-life adversity, in particular, maternal separation (MS) in rodents, demonstrate lasting deleterious effects on both the gut and the brain. Here, we review the effects of MS on both systems with a focus on stress-related behaviours. In addition, we discuss more recent findings showing the impact of gut-directed interventions, including nutrition with pre- and probiotics, illustrating the role played by gut microbiota in mediating the long-term effects of MS. Overall, preclinical studies suggest that nutritional approaches with pro- and prebiotics may constitute safe and efficient strategies to attenuate the effects of early-life stress on the gut–brain axis. Further research is required to understand the complex mechanisms underlying gut–brain interaction dysfunctions after early-life stress as well as to determine the beneficial impact of gut-directed strategies in a context of early-life adversity in human subjects.

This study investigated the effects of maternal separation on the feeding behavior of rats. A maternal separation model was used on postnatal day 1 (PND1), forming the following groups: in the maternal separation (MS) group, pups were separated from their mothers each day from PND1 to PND14, whereas in the control (C) group pups were kept with their mothers. Subgroups were formed to study the effects of light and darkness: control with dark and light exposure, female and male (CF and CM), and maternal separation with dark and light exposure, female and male (SDF, SDM, SLF and SLM). Female rats had higher caloric intake relative to body weight compared with male controls in the dark period only (CF=23.3±0.5 v. CM=18.2±0.7, P<0.001). Macronutrient feeding preferences were observed, with male rats exhibiting higher caloric intake from a protein diet as compared with female rats (CF=4.1±0.7, n=8 v. CM=7.0±0.5, n=8, P<0.05) and satiety development was not interrupted. Female rats had a higher adrenal weight as compared with male rats independently of experimental groups and exhibited a higher concentration of serum triglycerides (n=8, P<0.001). The study indicates possible phenotypic adjustments in the structure of feeding behavior promoted by maternal separation, especially in the dark cycle. The dissociation between the mother’s presence and milk intake probably induces adjustments in feeding behavior during adulthood.

We have evaluated in C57BL/6J mice the effect of maternal separation and post-weaning social isolation on ethanol intake, and on serotonin1A (5-HT1A) receptor function at the level of receptor–G protein interaction in the hippocampus and dorsal raphe nucleus. From postnatal days 2–14, litters were separated from the mother for 15 min (Handled) or for 180 min (Maternal separation). After weaning, pups were housed in pairs or in social isolation. At 2 months of age, ethanol intake and preference in mice were assessed using the two-bottle choice paradigm. Maternal separation increased ethanol preference in female mice that were subsequently housed in isolation. By contrast, post-weaning isolation increased ethanol preference and consumption in male mice regardless of pre-weaning rearing conditions. The increased ethanol preference and intake were limited to a 5% (v/v) concentration of ethanol. Our data suggest that adolescent mice are susceptible to the effects of post-weaning social isolation as shown by increased ethanol preference and consumption. Using quantitative autoradiography, 5-HT1A receptor number and function were determined by the binding of [3H]WAY-100635, and by [35S]GTPγS binding stimulated by the 5-HT1A receptor agonist 8-OH-DPAT, respectively. The binding experiments were done at approximately 3 months after the end of the two-bottle choice test in an attempt to minimize direct effects of ethanol drinking on 5-HT1A receptor function and number. 5-HT1A receptor-stimulated [35S]GTPγS binding in the dorsal raphe nucleus was increased in animals reared after weaning in isolation vs. in pairs, regardless of gender or pre-weaning rearing conditions. Our data suggest that there are long-term neurochemical consequences of social isolation of adolescent mice, specifically increased 5-HT1A receptor function in the dorsal raphe nucleus.