Download files
Abstract
Early trauma contributes to psychosocial disorders later in life. An adverse early environment induced by maternal separation is known to alter behavioural and stress responses in rats. The consumption of palatable food is known to dampen stress responses in animals, and emotions influence food choice in humans. We investigated the influence of palatable cafeteria high-fat diet (HFD) on behavioural responses following maternal separation or non handling, versus 15 minutes brief separation. After littering, Sprague-Dawley rats were exposed to short separation, S15 (15 minutes), prolonged separation, S180 (180 minutes) daily from postnatal days 2-14 or were non-handled. Pups were assigned to HFD or chow at weaning. We assessed depression and anxiety-like behaviour with sucrose preference test (SPT) and elevated plus maze (EPM) respectively, and measured hypothalamic corticotrophin releasing hormone (CRH) and hippocampal glucocorticoid receptor (GR) expression. S180 rats showed increased anxiety- and depression-like behaviors, with increased plasma corticosterone, hypothalamic CRH, and reduced hippocampal GR expression versus S15. These were normalized by provision of HFD. Similar effects were observed across gender, with greater beneficial effects in males. S15 showed no benefit of HFD. Non-handled female rats had less adverse impacts; HFD had beneficial impact on behavior in non-handled males. Thus both behavioural deficits and gene expression changes induced by early life stress were ameliorated by HFD. These results highlight the important place of palatable food in reducing central stress responses, supporting the therapeutic value of 'comfort food'.
Despite the beneficial effect of HFD on behavioural responses following maternal separation, the rats were metabolically disadvantaged with exaggerated plasma insulin concentrations compared to briefly separated rats under the same diet. Therefore in the second study, we investigated a healthier intervention using voluntary exercise. Exercise has been well documented to play a role in ameliorating depression and improving metabolic profile. Here we investigated the influence of palatable food and/or exercise on behavioural responses following early life stress in rats. Another cohort of rats was subjected to a similar maternal separation paradigm and soon after weaning rats were assigned to either receive chow, HFD, voluntary exercise via a running wheel (R), or combined HFD and R for 11 weeks. Anxiety-like behaviour was measured using light dark test (LDT) and EPM whereas depression-like behaviour was again assessed with the FST. Stress response was measured by investigating the rise in corticosterone during restraint stress. We measured GR, brain-derived neurotrophic factor (BDNF) and serotonin (5HT) 1A receptor mRNA in the hippocampus, and plasma hormones. Anxiety- and depression-like behaviour in S180 rats were ameliorated by the provision of HFD or R or HFD +R. HFD or R normalised the reduced expression of hippocampal GR, BDNF and 5HT1A mRNA and reduced stress response. S180 rats had similar body weight to S15, however their plasma insulin levels were quadrupled compared to the S15 rats when consuming HFD; adding exercise reduced plasma insulin concentrations.
While the effects of maternal separation on pups are well studied, the impact on dams has attracted little attention. Here we examined the early- and long-term impacts of maternal separation on behavioural profile of the dams, and the effects of HFD. After littering, Sprague-Dawley female rats were subjected to S180 or S15 from postnatal days 2-14. At 4 weeks postpartum, half the dams were assigned to HFD. Anxiety and depression-like behaviours were assessed pre and post-diet. Compared to S15 dams, S180 dams consuming chow demonstrated increased anxiety and depression-like behaviours assessed by EPM and FST tests respectively. These behavioural deficits were observed at 4 weeks, and persisted until 17 weeks postpartum. The S180 dams also had increased plasma corticosterone concentration compared to S15 dams, which coincided with increased hypothalamic CRH mRNA and reduced hippocampal GR mRNA expression, suggesting possible dysregulation of hypothalamic-pituitary-adrenal axis activity. Interestingly, continuous provision of HFD improved the behavioural deficits observed in S180 dams with significant reduction of hypothalamic CRH mRNA expression. These data are the first to describe long term detrimental behavioural impacts of separation in dams, suggesting this may provide a model of postpartum depression. Moreover, they support the notion of long-term beneficial effects of ‘comfort food’ on stress responses.
Taken together this work highlights the beneficial impact of palatable food or voluntary exercise in ameliorating the response to imposed stress. It has also explored potential mechanisms underlying these responses. As we have provided further data demonstrating that the early environment influences the adult phenotype, manipulation of the postnatal environment should be the target of future studies. For instance, further work should be directed at addressing the regional responses to these interventions, and testing the impact of shorter windows of intervention.