Individuals often eat calorically dense, highly palatable "comfort" foods during stress for stress relief. This article demonstrates that palatable food intake (limited intake of sucrose drink) reduces neuroendocrine, cardiovascular, and behavioral responses to stress in rats. Artificially sweetened (saccharin) drink reproduces the stress dampening, whereas oral intragastric gavage of sucrose is without effect. Together, these results suggest that the palatable/rewarding properties of sucrose are necessary and sufficient for stress dampening. In support of this finding, another type of natural reward (sexual activity) similarly reduces stress responses. Ibotenate lesions of the basolateral amygdala (BLA) prevent stress dampening by sucrose, suggesting that neural activity in the BLA is necessary for the effect. Moreover, sucrose intake increases mRNA and protein expression in the BLA for numerous genes linked with functional and/or structural plasticity. Lastly, stress dampening by sucrose is persistent, which is consistent with long-term changes in neural activity after synaptic remodeling. Thus, natural rewards, such as palatable foods, provide a general means of stress reduction, likely via structural and/or functional plasticity in the BLA. These findings provide a clearer understanding of the motivation for consuming palatable foods during times of stress and influence therapeutic strategies for the prevention and/or treatment of obesity and other stress-related disorders.corticosterone | anxiety-related behavior | synaptophysin | cAMP response element-binding protein | calcium/calmodulin-dependent protein kinase T he obesity epidemic is fueled by the easy availability of palatable, calorically dense foods amid an ever-escalating level of daily stress (1-3). Humans and rodents increase palatable food consumption when stressed (3-6), and the term "comfort food" is commonly used to signify possible stress-dampening properties of certain foods (particularly calorically dense foods containing high amounts of carbohydrates and/or fats). Indeed, comfort food intake in humans is linked with improved emotional states (7), and a high-carbohydrate diet is associated with reduced resting and stress-evoked cortisol levels (8-11).Stress (a real or perceived threat to homeostasis or well-being) typically evokes both physiological and emotional responses (reviewed in ref. 12). The physiological responses include activation of the hypothalamic-pituitary-adrenocortical (HPA) axis and the sympathetic branch of the autonomic nervous system. Activation of the sympathetic nervous system has numerous effects, including increases in heart rate and blood pressure. Activation of the HPA axis results in elevations in circulating adrenocorticotropic hormone (ACTH) and glucocorticoids (e.g., cortisol in humans and corticosterone in rats). Glucocorticoids have widespread action on numerous physiological processes, including mobilization of stored energy and maintenance of vascular tone. Perceived stressors also engage emotional respons...

The mammalian stress response is an integrated physiological and psychological reaction to real or perceived adversity. Glucocorticoids are an important component of this response, acting to redistribute energy resources to both optimize survival in the face of challenge and to restore homeostasis after the immediate challenge has subsided. Release of glucocorticoids is mediated by the hypothalamo-pituitary-adrenal (HPA) axis, driven by a neural signal originating in the paraventricular nucleus (PVN). Stress levels of glucocorticoids bind to glucocorticoid receptors in multiple body compartments, including the brain, and consequently have wide-reaching actions. For this reason, glucocorticoids serve a vital function in negative feedback inhibition of their own secretion. Negative feedback inhibition is mediated by a diverse collection of mechanisms, including fast, non-genomic feedback at the level of the PVN, stress-shut-off at the level of the limbic system, and attenuation of ascending excitatory input through destabilization of mRNAs encoding neuropeptide drivers of the HPA axis. In addition, there is evidence that glucocorticoids participate in stress activation via feed-forward mechanisms at the level of the amygdala. Feedback deficits are associated with numerous disease states, underscoring the necessity for adequate control of glucocorticoid homeostasis. Thus, rather than having a single, defined feedback ‘switch’, control of the stress response requires a wide-reaching feedback ‘network’ that coordinates HPA activity to suit the overall needs of multiple body systems.

Stress-related disorders such as anxiety and depression are disproportionately prevalent in women. Women are more likely to experience depression and anxiety disorders during periods of marked hormonal fluctuations, suggesting that gonadal hormones are involved in stress pathology. Depression and anxiety are both associated with aberrant secretion of glucocorticoids, which also show marked fluctuations across the reproductive cycle and in response to gonadal steroids. Thus, interactions between gonadal and stress hormones may play a major role in predisposing females to stress-related disease. The purpose of this brief review is to highlight preclinical data regarding the role of estrogens in depression and anxiety-like behaviors. While it is evident the exogenous estrogens modulate affective behavior in rodents, there is some disagreement in the literature, perhaps related to experimental designs that vary with respect to administration parameters and stress. Beneficial effects of estrogens on mood are most likely due to estrogen receptor (ER)β signaling. The antidepressant and anxiolytic effects of ERβ are consistent with its role in attenuating glucocorticoid responses to stress, suggesting that estrogens, acting at ERβ, may improve mood by suppressing glucocorticoid hyperactivity. However, additional studies demonstrate that ERβ signaling in the hippocampus is sufficient to induce antidepressant and anxiolytic behaviors. Thus, ERβ may improve mood via primary actions on hypothalamic (i.e., paraventricular nucleus) and/or extra-hypothalamic sites. Overall, the preclinical research suggests that selective ER modulators targeting ERβ may be an attractive alternative or adjunct treatment to currently prescribed antidepressants or anxiolytics.

Background Stress-related disorders (e.g., depression) are associated with hypothalamic-pituitary-adrenocortical axis dysregulation and prefrontal cortex (PFC) dysfunction, suggesting a functional link between aberrant prefrontal corticosteroid signaling and mood regulation. Methods We used a virally mediated knockdown strategy (short hairpin RNA targeting the glucocorticoid receptor [GR]) to attenuate PFC GR signaling in the rat PFC. Adult male rats received bilateral microinjections of vector control or short hairpin RNA targeting the GR into the prelimbic (n = 44) or infralimbic (n = 52) cortices. Half of the animals from each injection group underwent chronic variable stress, and all were subjected to novel restraint. The first 2 days of chronic variable stress were used to assess depression- and anxiety-like behavior in the forced swim test and open field. Results The GR knockdown confined to the infralimbic PFC caused acute stress hyper-responsiveness, sensitization of stress responses after chronic variable stress, and induced depression-like behavior (increased immobility in the forced swim test). Knockdown of GR in the neighboring prelimbic PFC increased hypothalamic-pituitary-adrenocortical axis responses to acute stress and caused hyper-locomotion in the open field, but did not affect stress sensitization or helplessness behavior. Conclusions The data indicate a marked functional heterogeneity of glucocorticoid action in the PFC and highlight a prominent role for the infralimbic GR in appropriate stress adaptation, emotional control, and mood regulation.

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