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.

Keywords: HPA-axis; dopamine receptors; juvenile stress; metabolic syndrome; nucleus accumbens; palatable food; prefrontal cortex; social interaction.

Figure 1

Singly housed animals were assigned to four groups: (1) Chow + Stress; (2) Palatable + Stress; (3) Chow + No Stress and (4) Palatable + No Stress. Groups assigned to the stressor condition were exposed to a different episodic stressor per day from postnatal days (PD) 27–29 while non-stressed animals received daily handling. The following were evaluated in adulthood: Group 1—40 animals (n = 10 per group) were tested for behavior (social interaction), adiposity and gene expression. Group 2—48 animals (n = 12 per group) were tested for hypothalamic-pituitary-adrenal (HPA) activity after an acute stressor (air-puff) and for glucose tolerance.

Figure 2

Effect of access to a palatable diet and juvenile stressor exposure on total caloric intake, chow and palatable diet consumption and caloric intake (adjusted to body weight), palatable diet preference and weight gained. (A) Access to a palatable diet and juvenile stressor exposure increased total caloric intake on PD 50. (B) Access to a palatable diet led to an overall lower chow consumption across age. (C) Palatable diet consumption did not differ regardless of stressor exposure. (D) Across development, juvenile stressor exposure did not elicit a preference for a palatable diet. (E) Caloric intake did not differ on PD 30 between groups right after 3-day juvenile stressor exposure (PD 27–29). (F) Juvenile stressor exposure decreased caloric intake in late adolescence (PD 55) and this did not occur in rats that consumed the palatable diet. ^αSignificantly different from non-stressed palatable diet fed group (p < 0.05). ^τSignificantly different to chow diet groups (p < 0.05). *Significantly different from stressed palatable diet group and non-stressed chow group (p < 0.05).

Figure 3

Effect of access to a palatable diet and juvenile stressor exposure on body weight and adiposity. (A) Consumption of a palatable diet led to greater body weight on PD 70. (B) There were no significant differences in weight gained from PD 27–30 shortly after juvenile stressor exposure (C) Access to the palatable diet increased overall weight gained from PD 21–70. (D) Access to a palatable diet increased total adiposity in juvenile stressed rats only. (E) Access to a palatable diet and juvenile stressor exposure increased subcutaneous fat, whereas access to a palatable diet increased retroperitoneal and brown fat. ^τSignificantly different to chow diet groups (p < 0.05). ^#Significantly different from other conditions (p < 0.05).

Figure 4

Effects of access to a palatable diet and juvenile stressor exposure on glucose tolerance and HPA-axis response to a mild stressor. (A) Juvenile stressor exposure increased corticosterone levels at baseline and 20 min after an air-puff stressor in adult chow-fed rats but not in rats that had access to the palatable diet. Air-puff administered at t = 0 as indicated and the volume of each punch was 2.5 μL. (B) Glucose levels were elevated at 15, 30 and 60 min after intraperitoneal administration of dextrose (0.75 g/mL) at t = 0 min, as indicated, in all groups. However, there was no significant effect of diet or stress conditions. ^#Significantly different from other conditions (p < 0.05).

Figure 5

Access to a palatable diet prevents the decrease in social interaction in adulthood elicited by juvenile stressor exposure. (A) Adult rats exposed to juvenile stress exhibited an overall reduction in total social interaction and this effect was reversed in palatable diet fed rats. (B) Locomotor activity (# of squares crossed) was comparable across groups. (C) Juvenile stressor exposure decreased sniffing and over/under behaviors. ^#Significantly different from other conditions (p < 0.05).

Figure 6

Effect of juvenile stress and diet on fold changes for dopamine (DA) receptors mRNA expression in the prefrontal cortex (PFC) and nucleus accumbens (NA). (A) There were no significant changes in DRD1 expression across groups in the PFC. (B) DRD2 expression in the PFC was downregulated in non-stressed rats fed the palatable diet. (C) There was an upregulation in DRD1 expression in juvenile stressed rats with access to palatable food in the NA (D) DRD2 expression was upregulated in juvenile stressed rats with access to palatable food however this did not reach significance in the NA. *Significantly different from stressed palatable diet group and non-stressed chow group (p < 0.05). ^αSignificantly different from non-stressed palatable diet group (p < 0.05). ^εSignificantly different from non-stressed groups (p < 0.05).