Palatable food reduces anxiety-like behaviors and HPA axis responses to stress in female rats in an estrous-cycle specific manner

Abstract Eating tasty foods dampens responses to stress – an idea reflected in the colloquial term ‘comfort foods’. To study the neurobiological mechanisms by which palatable foods provide stress relief, we previously characterized a limited sucrose intake (LSI) paradigm in which male rats are given twice-daily access to 4 ml of 30% sucrose solution (vs. water as a control), and subsequently have reduced hypothalamic-pituitary-adrenocortical (HPA) axis responsivity and anxiety-related behaviors. Notably, women may be more prone to ‘comfort feeding’ than men, and this may vary across the menstrual cycle, suggesting the potential for important sex and estrous cycle differences. In support of this idea, LSI reduces HPA axis responses in female rats during the proestrus/estrus (P/E), as opposed to the diestrus 1/diestrus 2 (D1/D2) estrous cycle stage. However, the effect of LSI on anxiety-related behaviors in females remains unknown. Here we show that LSI reduced stress-related behaviors in female rats in the elevated plus-maze and restraint tests, but not in the open field test, though only during P/E. LSI also decreased the HPA axis stress response primarily during P/E, consistent with prior findings. Finally, cFos immunolabeling (a marker of neuronal activation) revealed that LSI increased post-restraint cFos in the central amygdala medial subdivision (CeM) and the bed nucleus of the stria terminalis posterior subnuclei (BSTp) exclusively during P/E. These results suggest that in female rats, palatable food reduces both behavioral and neuroendocrine stress responses in an estrous cycle-dependent manner, and the CeM and BSTp are implicated as potential mediators of these effects.