Stress exposure, food intake and emotional state

Abstract

This manuscript summarizes the proceedings of the symposium entitled, "Stress, Palatable Food and Reward", that was chaired by Drs. Linda Rinaman and Yvonne Ulrich-Lai at the 2014 Neurobiology of Stress Workshop held in Cincinnati, OH. This symposium comprised research presentations by four neuroscientists whose work focuses on the biological bases for complex interactions among stress, food intake and emotion. First, Dr Ulrich-Lai describes her rodent research exploring mechanisms by which the rewarding properties of sweet palatable foods confer stress relief. Second, Dr Stephanie Fulton discusses her work in which excessive, long-term intake of dietary lipids, as well as their subsequent withdrawal, promotes stress-related outcomes in mice. Third, Dr Mark Wilson describes his group's research examining the effects of social hierarchy-related stress on food intake and diet choice in group-housed female rhesus macaques, and compared the data from monkeys to results obtained in analogous work using rodents. Finally, Dr Gorica Petrovich discusses her research program that is aimed at defining cortical-amygdalar-hypothalamic circuitry responsible for curbing food intake during emotional threat (i.e. fear anticipation) in rats. Their collective results reveal the complexity of physiological and behavioral interactions that link stress, food intake and emotional state, and suggest new avenues of research to probe the impact of genetic, metabolic, social, experiential and environmental factors on these interactions.

Keywords: Anorexia; HPA axis; anxiety; comfort food; depression; obesity.

Figure 1

A history of limited sucrose intake reduces behavioral and physiological responses to stress. (A) In a social interaction test of behavioral anxiety, rats with a history of limited sucrose (S) drink spent a greater proportion of time interacting socially with a novel conspecific relative to water (W) controls, regardless of whether they received an acute restraint stress (Restraint) or not (No Restraint) immediately prior to the social interaction test (left). *p < 0.05 vs. water controls. This increased social interaction was similar to that which occurs after treatment with the known anxiolytic diazepam (D) vs. vehicle (V) (right). *p < 0.05 vs. vehicle. (B) The tachycardic response to acute restraint was reduced by limited sucrose drink relative to water controls. *p < 0.05 vs. water controls. Data are shown as mean ± SEM. Reproduced from (Ulrich-Lai et al., 2010).

Figure 2

A history of limited sucrose intake reduces hypothalamic-pituitary-adrenal (HPA) axis responses to stress and is largely mediated by the pleasurable and rewarding properties of the sucrose. (A) The plasma adrenocorticotropic hormone (ACTH) response to a 20-min restraint stress is blunted by either limited sucrose (Suc; 30%) or saccharin (Sac; 0.1%; a non-caloric, artificial sweetener) drink intake, suggesting that the pleasurable or rewarding properties of these sweet drinks are sufficient for stress relief. *p < 0.05 vs. Water (Wat). (B) Rats given twice-daily sucrose (S) drink have a reduced integrated (area-under-the-curve) plasma corticosterone response to restraint relative to water-only controls (left). In contrast, those receiving twice-daily orogastric gavage of 4 ml of sucrose vs. water (to replicate many of the post-ingestive effects of the drink while minimizing taste and hedonic properties), do not have a reduced plasma corticosterone response (right), suggesting that sucrose’s hedonic/rewarding properties are necessary. *p < 0.05 vs. Water. (C) Male rats with a history of daily, limited (30 min) access to a sexually-responsive female engaged in sexual activity (Sex) and had a reduced integrated plasma corticosterone response to restraint compared to both undisturbed controls (C) and sham-sex rats (Sh; this group received a female rat in their cages, but the female was enclosed in a wire mesh box that prevented physical interactions), suggesting that other types of natural reward provide similar HPA-dampening. *p < 0.05 vs. control and sham. Data are shown as mean ± SEM. Reproduced from (Ulrich-Lai et al., 2010).

Figure 3

Neuronal activity in the basolateral amygdala (BLA) is necessary for hypothalamic-pituitary-adrenal (HPA) axis-dampening by limited sucrose intake. The plasma corticosterone response to restraint stress was assessed after sucrose (S) vs. water (W) intake in rats with bilateral vehicle-injected, intact BLA (Intact), or bilateral ibotenate infusion that produced lesions that either missed (Miss) or hit (Lesion) the BLA. (A) Representative images of neuron-specific nuclear protein (NeuN)-immunolabeling in the BLA of Intact and Lesion rats. CeA = central amygdala, MeA = medial amygdala, opt = optic tract. Scale bar = 500 um. (B) Sucrose reduced the integrated (area-under-the-curve) plasma corticosterone response to restraint stress (relative to water control rats) in Intact and Miss rats, while this HPA-dampening did not occur in rats with bilateral BLA lesion (Lesion). *p < 0.05 vs. water controls, #p < 0.05 vs. Intact-Sucrose and Miss-Sucrose. Data are shown as mean ± SEM. Reproduced from (Ulrich-Lai et al., 2010).

Figure 4. Diet-induced depressive-like behavior

(A) Percentage of time spent in open arms of the elevated plus maze (EPM) was significantly reduced in high fat diet (HFD)-fed mice as compared to control low fat diet (LFD)-fed mice. (B) Significant increase in time spent in center of open field in HFD mice compared to control LFD mice. (C) Effect of chronic consumption of HFD on depressive behaviour expressed as immobility time in the forced swim test (FST) conducted in a separate cohort of mice. (D) Spontaneous locomotor activity expressed as total distance traveled during 15 min in a metabolism cage in C57Bl6 LFD and HFD mice (n = 6 each group). Mean±SEM *p < 0.05. Figure from (Sharma and Fulton, 2013).

Figure 5. High-fat diet (HFD) withdrawal (dieting) increases anxiety, stress and palatable food craving

(A) Elevated plus maze (EPM) open arm time was significantly reduced in mice withdrawn from HFD as compared to mice withdrawn from low fat diet (LFD). (B) Elevated basal plasma corticosterone (CORT) concentration in HFD withdrawn mice as compared to LFD withdrawn mice. (C) Body weights decreased post-withdrawal in mice subjected to HFD withdrawal (WD: day of withdrawal). (D) Withdrawal from HFD, but not LFD, significantly increased breakpoint thresholds for sucrose rewards (indicating increased motivation for sucrose reward) as of day 3 of withdrawal (WD D3). Breakpoints remained elevated on day 4 and 5 of withdrawal when sucrose rewards were replaced by high-fat food rewards. Mean ± SEM; *p ≤ 0.05, **p ≤ 0.001. Figure from (Sharma et al., 2013b).

Figure 6. Average (± SEM) daily caloric intake for dominant and subordinate female rhesus monkeys from both a low caloric (LCD) and high caloric diet (HCD). Redrawn from (Arce et al., 2010, Michopoulos et al., 2012c)

Figure 7

Comparison of average (± SEM) meal size (kcal), meal number, and calories from snacks for dominant and subordinate female rhesus monkeys maintained in a dietary environment where both a low caloric (LCD) and high caloric diet (HCD) are available. Redrawn from (Moore et al., 2013).

Figure 8

Average (± SEM) daily caloric intake of both a low caloric (LCD) and high caloric diet (HCD) in dominant and subordinate female rhesus monkeys during two days of placebo and two days of treatment with the corticotropin releasing factore receptor type 1 (CRF-R1) antagonist, Antalarmin. Subordinate but not dominant females showed a significant attenuation in caloric intake during Antalarmin treatment. Reprinted from (Moore et al., 2015).

Figure 9

(A) Food consumption (mean ± SEM) of male and female rats during tests with fear cue presentations. During training, rats in the conditioned groups received tones paired with footshocks, while rats in the control groups received tones but no shocks. Tests were conducted on separate days, under acute food deprivation (no footshocks given during tests). Significant differences (p < 0.05) between Conditioned and Control groups are indicated by * for females and by the # for males. (B) Conditioned freezing behavior during food consumption tests. Graphs show percentages (mean ± SEM) of the total time spent freezing during the tests. Adapted from (Petrovich and Lougee, 2011), with permission.

Figure 10

Summary schematic illustrating the complex inter-relationships between stress and ingestive behavior, and highlighting the overall approach and key findings of each symposium speaker.