Palatable Food Dampens the Long-Term Behavioral and Endocrine Effects of Juvenile Stressor Exposure but May Also Provoke Metabolic Syndrome in Rats

Abstract

The juvenile period is marked by a reorganization and growth of important brain regions including structures associating with reward seeking behaviors such as the nucleus accumbens (NA) and prefrontal cortex (PFC). These changes are impacted by stressors during the juvenile period and may lead to a predisposition to stress induced psychopathology and abnormal development of brain reward systems. Like in humans, adult rodents engage certain coping mechanisms such as increases in the consumption of calorie-rich palatable foods to reduce stress, but this behavior can lead to obesity and metabolic disorders. In this study, we examined whether stressors during the juvenile period led to increased caloric intake when a palatable diet was accessible, and whether this diet attenuated adult stress responses. In addition, we examined if the stress buffering effects produced by the palatable diet were also accompanied by an offset propensity towards obesity, and by alterations in mRNA expression of dopamine (DA) receptors in the NA and PFC in adulthood. To this end, juvenile male Wistar rats underwent episodic stressor exposure (forced swim, elevated platform stress and restraint) on postnatal days (PD) 27–29 and received access to regular chow or daily limited access to a palatable diet until adulthood. At the age of 2 months, rats were tested on a social interaction test that screens for anxiety-like behaviors and their endocrine responses to an acute stressor. Animals were sacrificed, and their brains processed to detect differences in DA receptor subtype expression in the PFC and NA using qPCR. Results showed that rats that were stressed during the juvenile period displayed higher social anxiety and a sensitized corticosterone response as adults and these effects were attenuated by access to the palatable diet. Nevertheless, rats that experienced juvenile stress and consumed a palatable diet showed greater adiposity in adulthood. Interestingly, the same group displayed greater mRNA expression of DA receptors at the NA. This suggests that access to a palatable diet mitigates the behavioral and endocrine effects of juvenile stressor exposure in adulthood, but at the cost of metabolic imbalances and a sensitized dopaminergic system.

Pathways to depression: Dynamic associations between neural responses to appetitive cues in the environment, stress, and the development of illness

“…One possibility, which we are currently pursuing in the lab, is that blunted neural responses to appetitive cues are associated with reduced motivation to pursue positive experiences and outcomes in the environment, like high‐calorie foods, or social contact with others (Auerbach et al, 2014; Meehl, 2001). Because these positive experiences and outcomes have been shown to buffer against many of the adverse effects of stress exposure (Ali et al, 2018; Hostinar et al, 2014), reduced motivation to pursue rewards or the company of loved ones during times of prolonged stress, when available reinforcers are limited, may further limit individuals' capacity to cope adaptively with stressors. In what follows, I will focus on our work with the RewP to illustrate this line of research.…”

Western Diet Consumption During Development: Setting the Stage for Neurocognitive Dysfunction

“…For instance, in male rats, consumption of a high sucrose WD during social isolation from PN 21–28 resulted in reduced anxiety-like behavior in the OF and EPM tests at PN 28 relative to animals that received standard chow and animals that received stress without the WD ( Marcolin et al, 2012 ). Similarly, social anxiety was attenuated in male rats maintained on a WD (45% kcal from fat) after weaning after having previously undergone a 3-day ELS test from PN 27–29 where on each day they were subjected to either forced swim, elevated platform stress, or restraint adulthood ( Ali et al, 2018 ). In male rats subjected to limited nesting from PN 2–9, free access to a high fat/high sucrose diet (43% kcals fat, 17% kcals protein and 40% kcals from sucrose) initiated at weaning also prevented the expression of an anxiety phenotype at adulthood ( Maniam et al, 2016 ).…”

“…While the underlying mechanisms for the anxiolytic effects of WD consumption in cases of ELS are incompletely understood, WD consumption, either during or following ELS, resulted in rats consuming more food ( Marcolin et al, 2012 ; Maniam et al, 2016 ), gaining more weight ( Maniam and Morris, 2010 ; Marcolin et al, 2012 ; Maniam et al, 2016 ), having increased adipose tissue ( Maniam and Morris, 2010 ; Ali et al, 2018 ), higher plasma glucose levels ( Marcolin et al, 2012 ), and elevated plasma leptin and insulin ( Maniam and Morris, 2010 ). Normally ELS will result in an elevated corticosterone response, however, consumption of WD following ELS reduces the corticosterone response in adulthood ( Maniam and Morris, 2010 ; Ali et al, 2018 ). The reduced corticosterone response may be related to the normalized hypothalamic corticosterone releasing hormone mRNA and reduced hippocampal glucocorticoid receptor gene expression seen in adulthood following consumption of a WD in females ( Maniam and Morris, 2010 ), although hippocampal glucocorticoid receptor protein expression was increased in males ( Maniam et al, 2016 ).…”

“…The reduced corticosterone response may be related to the normalized hypothalamic corticosterone releasing hormone mRNA and reduced hippocampal glucocorticoid receptor gene expression seen in adulthood following consumption of a WD in females ( Maniam and Morris, 2010 ), although hippocampal glucocorticoid receptor protein expression was increased in males ( Maniam et al, 2016 ). Moreover, WD may prevent an imbalance of antioxidant enzymes in the PFC ( Marcolin et al, 2012 ) or lead to increased D1R and D2R mRNA expression in the ACB, suggesting that dopamine signaling may also have a role in protecting against stress-induced anxiety-like behavior ( Ali et al, 2018 ). Importantly, these studies suggest that ELS in combination with a WD prevents anxiety-like behavior despite leading to a compromised metabolic phenotype, as demonstrated by weight gain, adiposity, and elevated plasma insulin, leptin, and glucose levels.…”

Obesity and dietary fat influence dopamine neurotransmission: exploring the convergence of metabolic state, physiological stress, and inflammation on dopaminergic control of food intake

“…Ultimately, palatable food intake acutely increases dopamine release and reuptake, but extended HFD intake reduces the capacity for dopamine neurotransmission. These trends are related to the physiological Plasma CORT Anxio-depressive response 159,178,195 During HFD Removal…”