Shlomi Cohen, a Psychology PhD student working under the guidance of Prof. Hagit Cohen, the Director of the Stress and Anxiety Research Unit in BGU's Faculty of Health Sciences, has demonstrated in a series of experiments that animals are more vulnerable to stress during the night and, conversely, more resilient in the morning.
The reaction to stress is characterized by the release of important hormones such as glucocorticoids (cortisol in human and corticosterone in rodents) (released following brain signaling to the adrenal cortex; the hypothalamic-pituitary-adrenal (HPA) axis) that enable the organism to prepare for, respond to, and cope with the acute demands of physical and emotional stressors (fight or flight). The appropriate corticosterone release, commensurate with stressor severity, enables the body to properly contain stress responses so as to promote recovery. Indeed, inadequate corticosterone release following stress not only delays recovery but can also interfere with the processing or interpretation of stressful information and alters the trajectory of trauma exposure. It is well known that the HPA-axis displays a characteristic circadian pattern of corticosterone release, with higher levels at the beginning of the morning and lower levels at the beginning of the night. Since corticosterone levels modify the response to stress and influence the susceptibility to and/or severity of stress-related sequelae, the effects of an acute psychological trauma applied at different times on behavioral stress responses were examined.
The researchers’ findings were recently published in the Neuropsychopharmacology Journal. Rats were exposed to stress either at the beginning of the night or at the beginning of the morning. Their behaviors were assessed seven days post-exposure for retrospective classification into behavioral response groups. The results clearly demonstrated that the time of day at which traumatic exposure occurred altered the sequelae of the trauma – the time of day of the traumatic exposure markedly affected the pattern of the behavioral stress response and the prevalence of rats showing an extreme behavioral response (PTSD-like behavioral responses). Rats exposed to the stressor at the beginning of their inactive phase (night) displayed a more traumatic behavioral response, and, conversely, were more resilient to stress exposure at the beginning of the active phase i.e. in the morning.
To evaluate if the behavioral response was commensurate with their respective HPA axis profiles, the authors assessed the influence of stress exposure at the beginning of the morning or night on plasma corticosterone levels. To their surprise, the researchers found that although the basal levels of corticosterone were significantly different between the morning and night, reflecting the expected circadian variation, the magnitude of the HPA axis response to stress was not statistically different between the times.
“The magnitude of the corticosterone response to stress was not statistically different between the times. However, a slower return to baseline corticosterone levels after stress exposure was observed in the morning. In other words, during stress exposure in the morning, high corticosterone levels are prolonged in comparison to stress exposure at night. These findings imply a possible association between the circadian phase, HPA regulation, and the behavioral response to stress. We found that corticosterone levels were significantly increased at around the same time in which the rise in NPY levels was observed in the hypothalamus. This finding suggests a possible association between central NPY levels and circulating corticosterone levels,” according to Prof. Cohen.
Rats exposed to the stressor during the night displayed faster post-exposure corticosterone decay and a more pronounced stress-induced decline in neuropeptide Y (NPY) expression in the hypothalamus. Blocking hypothalamic NPY prior to stress applied in the morning, or administering NPY to the hypothalamus prior to stress applied in the night, had a resounding behavioral effect.
The authors thus suggest that the diurnal variations in HPA and NPY significantly affect the behavioral response, conferring more resilience at the beginning of the morning and more vulnerability at the beginning of the night, implying that NPY plays a significant role in conferring resilience to stress-related psychopathology.
