Daily limited access to sweetened drink attenuates hypothalamic-pituitary-adrenocortical axis stress responses

Abstract

Stress can promote palatable food intake, and consumption of palatable foods may dampen psychological and physiological responses to stress. Here we develop a rat model of daily limited sweetened drink intake to further examine the linkage between consumption of preferred foods and hypothalamic-pituitary-adrenocortical axis responses to acute and chronic stress. Adult male rats with free access to water were given additional twice-daily access to 4 ml sucrose (30%), saccharin (0.1%; a noncaloric sweetener), or water. After 14 d of training, rats readily learned to drink sucrose and saccharin solutions. Half the rats were then given chronic variable stress (CVS) for 14 d immediately after each drink exposure; the remaining rats (nonhandled controls) consumed their appropriate drinking solution at the same time. On the morning after CVS, responses to a novel restraint stress were assessed in all rats. Multiple indices of chronic stress adaptation were effectively altered by CVS. Sucrose consumption decreased the plasma corticosterone response to restraint stress in CVS rats and nonhandled controls; these reductions were less pronounced in rats drinking saccharin. Sucrose or saccharin consumption decreased CRH mRNA expression in the paraventricular nucleus of the hypothalamus. Moreover, sucrose attenuated restraint-induced c-fos mRNA expression in the basolateral amygdala, infralimbic cortex, and claustrum. These data suggest that limited consumption of sweetened drink attenuates hypothalamic-pituitary-adrenocortical axis stress responses, and calories contribute but are not necessary for this effect. Collectively the results support the hypothesis that the intake of palatable substances represents an endogenous mechanism to dampen physiological stress responses.

Figure 1

Timeline of the experimental design. On day 1, rats began drink training consisting of twice daily access (09:00 and 15:00) to sippers containing 4 ml of water, saccharin (0.1%), or sucrose (30%). On days 15–28, half of the rats were given twice daily exposure to an unpredictable stressor (chronic variable stress; CVS) immediately after receiving their respective drink solutions. Nonhandled control rats continued to receive their respective drink solutions but did not receive CVS. On the morning of day 29, rats did not receive their drink solutions and were challenged with a novel restraint stress.

Figure 2

Rats readily learned to drink sucrose and saccharin and intake was reduced during chronic stress. Time course of mean daily drink intake (8 ml/day maximum) for Control (top) and CVS (bottom) rats receiving sucrose, saccharin or water twice daily via sippers (in addition to ad lib access to food and water). #p<0.05 vs Control. †p<0.05 vs previous time point. Not noted on figure: all sucrose and saccharin values are different from water. n=8–9/group.

Figure 3

The plasma ACTH response to restraint (20-min) was augmented by prior CVS exposure and not affected by type of drink. The time course of restraint-stress induced plasma ACTH for Control (A) and CVS (B) rats receiving sucrose, saccharin or water twice daily via sippers (in addition to ad lib access to food and water). #p<0.05 vs Control. Not noted on figure: all values at 20, 40, and 60 min are greater than 0 min. (C) The integrated (area under the curve, AUC) plasma ACTH response to restraint. A= main effect of CVS vs Control. n=7–9/group.

Figure 4

The plasma corticosterone response to restraint was attenuated by sucrose and saccharin drink in Control rats, and CVS facilitated the plasma corticosterone response to restraint regardless of type of drink. The time course of restraint-stress induced plasma corticosterone for Control (A) and CVS (B) rats receiving sucrose, saccharin or water twice daily via sippers (in addition to ad lib access to food and water). (C) The integrated (area under the curve, AUC) plasma corticosterone response to restraint. *p<0.05 vs water, #p<0.05 vs Control. Not noted on figure: all values at 20, 40, and 60 min are greater than 0 min. n=7–9/group. Please note that the statistics depicted on the figure resulted from a three-way ANOVA comparing DRINK, CVS, and TIME. A separate planned 2-way ANOVA at the 0-min time point revealed a main effect of CVS to increase basal plasma corticosterone, which is not indicated on the figure.

Figure 5

Food intake was decreased by sucrose drink, and CVS reduced food intake regardless of type of drink. The time course of average daily food intake for Control (left) and CVS (right) rats receiving sucrose, saccharin or water twice daily via sippers (in addition to ad lib access to food and water). *p<0.05 vs water, #p<0.05 vs Control, †p<0.05 vs water and saccharin. Not noted on figure: 15–29 days is different from 1–14 days for all groups except Saccharin Control. n=8–9/group.

Figure 6

Body weight gain was attenuated by CVS regardless of type of drink. The time course of increased body weight for Control (left) and CVS (right) rats receiving sucrose, saccharin or water twice daily via sippers (in addition to ad lib access to food and water). *p<0.05 vs water and sucrose, # p<0.05 vs Control. Not noted on figure: 15–29 days is different from 1–14 days for all groups except Sucrose CVS. n= 8–9/group.

Figure 7

Example images of CRH mRNA expression as assessed by in situ hybridization. (A) paraventricular nucleus of the hypothalamus (PVN), (B) central nucleus of the amygdala (CeA), and (C) oval and fusiform subregions of the bed nucleus of the stria terminalis (ovBST and fuBST, respectively).

Figure 8

Example images of c-fos mRNA expression as assessed by in situ hybridization. (A) claustrum (Cl) and orbitofrontal cortex (OFC); (B) anterior cingulate (AC), prelimbic (PrL), and infralimbic (IL) subregions of medial prefrontal cortex; (C) intermediate lateral septum (iLS), posterior gustatory cortex (pGC), and piriform cortex (Pir); (D) ventral lateral septum (vLS), anterodorsal preoptic nucleus (ADP), and ventrolateral medial preoptic area (vlMPOA); (E) paraventricular nucleus of the hypothalamus (PVN) and lateral hypothalamic area (LH); (F) CA1, CA3 and dentate gyrus (DG) subregions of the hippocampus, basolateral amygdala (BLA), medial amygdala (MeA) and dorsomedial nucleus of the hypothalamus (DMH).