The Effects of Chronic Variable Stress and Photoperiod Alteration on the Hypothalamic–Pituitary–Adrenal Axis Response and Behavior of Mice

Chronically stressed male and female mice show a similar peripheral and central pro-inflammatory profile after an immune challenge

“…The present CVS paradigm did not induce hypertrophy of the adrenal glands and involution of the thymus, in line with previous findings from our laboratory using the same protocol [ 32 ]. Hypertrophy of the adrenals and involution of the thymus are considered hallmarks of long-term stress exposure in rodents.…”

“…Abolishing TNF-α production in these animals mitigated the stress-induced anxiety changes [ 61 ]. Previous behavioral findings from our laboratory indicated that exposure to the present CVS protocol also induced anxiety-like changes in both male and female mice [ 32 ]. The current results, therefore, suggest a potential neuroimmune alteration underlying these phenotypical changes induced by chronic stress.…”

“…The reduction in body weight gain observed in male animals is in line with previous findings showing attenuation of body weight gain in chronically stressed rodents [ 2 , 17 , 24 , 40 , 41 , 47 , 48 ]. Thought previous studies, including one from our laboratory, suggested that chronic stress attenuates body weight gain also in female rodents [ 17 , 24 , 32 , 49 ], there is evidence that chronically stressed male and female mice might gain weight after chronic social defeat [ 50 , 51 ], suggesting that the metabolic effects of stress exposure might be linked with the nature of the stressors regimen. Also, female mice showed increased intake of highly palatable food after 2 weeks of a CVS paradigm, revealing an increased sensitivity of food-seeking behaviors in females compared to males [ 52 ].…”

“…Animals were exposed to the stressors in a separated room, and control mice remained undisturbed in the colony room. The stressors in the CVS paradigm were the same used on a previous work from our group [ 32 ], and included a selection of stressors that varied in nature and duration. During stress exposure, the enrichment devices in the animal’s home cages were removed.…”

“…For instance, female rodents have higher resting and stress-induced CORT [ 27 – 29 ] and ACTH [ 30 ] levels than males. Sex differences are also observed in the expression of neuropeptides in the paraventricular nucleus of the hypothalamus [ 31 ], as well as in the mRNA levels of key regulators of the HPA axis activity [ 32 ]. Moreover, sex differences in the priming effects of acute stressors on the neuroinflammatory responses have been previously reported, with prior exposure to stress sensitizing the cytokine levels in the microglia of males, while stimulating serum IL-1β production in females after an immune challenge [ 16 ].…”