Voluntary exercise and palatable high-fat diet both improve behavioural profile and stress responses in male rats exposed to early life stress: role of hippocampus.

Childhood trauma induced by adverse early life experience is associated with increased risk of psychological disorders in adulthood. Disruption of normal development has been shown to affect hippocampal morphology and function, influencing adaptations to stress. Here we investigated whether palatable food and/or exercise would ameliorate the behavioural responses following early life stress in rats. Rats were subjected to 15 (S15) or 180 (S180) minutes separation from dams on postnatal days 2-14. After weaning, rats were assigned to either receive chow (C), high-fat diet (HFD), voluntary exercise (running, R), or combined HFD and R for 11 weeks. In addition to anxiety- and depression-like behaviours, response to restraint stress was measured. Glucocorticoid receptor (GR), brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine receptor 1A (5HT1A) receptor mRNA in the hippocampus were measured. S180 rats had similar body weight to S15, however their plasma insulin concentrations were double those of S15 rats when consuming HFD; adding exercise reduced plasma insulin. Anxiety-like behaviour in S180 rats, measured using Light Dark test (LDT) and Elevated Plus Maze (EPM) were ameliorated by the provision of HFD, R or HFD+R. A similar effect was observed on depression-like behaviour assessed by forced swim test (FST), with less time being spent immobile. Exposure to early-life stress during development was associated with significant reductions in hippocampal GR, 5HT1A receptor and BDNF mRNA, and these changes were normalized in S180 rats provided with HFD or exercise. Prolonged maternal separation resulted in exacerbated hyperinsulinemia when consuming HFD suggesting that these rats are metabolically disadvantaged. In summary, voluntary exercise alone or in combination with HFD produced beneficial effects on both behaviour and metabolic outcomes in rats exposed to early life stress. Crown