Sleep deprivation and stress: an inseparable pair

Prolonged sleep deprivation (SD) represents a stressful event for it activates the neuroendocrine stress response, as reflected by increased plasma levels of adrenaline, adrenocorticotropic hormone (ACTH) and corticosterone. However, the extent to which SD activates the hypothalamic‐pituitary‐adrenal (HPA) axis can be modulated by environmental factors. Using two versions of the platform method ‐ individual or group SD for 96h, we observed that group support reduces anxiety‐like behavior of animals in the elevated plus maze and, consequently, the stimulation of the HPA axis in response to this test. In a second study, we tested the influence of palatable solutions to reduce SD‐stimulated HPA axis activity. Although SD continued to result in high adrenocorticotropic hormone (ACTH) and corticosterone (CORT) plasma levels, animals provided with saccharin or sucrose (palatable) solutions exhibited lower hormone levels than those provided with water. Despite the fact that sleep‐deprived rats consumed a large amount of sucrose solution, they still consumed more chow than their control counterparts and lost just as much weight as the water‐provided sleep‐deprived group, indicating augmented energy expenditure. We pursued the mechanisms that could contribute to such an intense metabolic change and found that insulin levels were greatly reduced after SD and remained low after 96h of sleep recovery, whereas CORT levels were elevated at the end of SD and remained so after sleep recovery. Interestingly, the loss of body weight was due to loss of fat mass, but not to protein in the carcass. Finally, we looked at the feeding pattern and immunoreactivity (ir) of CRH and orexin in the hypothalamus of sleep‐deprived rats. The results showed that sleep‐deprived rats ate more during the daytime than control rats, ACTH and CORT levels were higher than in control rats throughout the entire period of SD and that both CRH and orexin‐ir were increased. The loss of body weight appeared to be related to elevated CORT levels, insofar as chronic administration of metyrapone (a CORT synthesis inhibitor) prevented this phenomenon. In conclusion, this set of data suggests that SD activates the HPA axis in its entirety, despite the modulatory influence of environmental factors. In addition, increased orexin‐ir appears to be involved with both stress and feeding responses induced by SD. Financial support provided by grants from Fundação de Amparo àPesquisa do Estado de São Paulo (FAPESP ‐ CEPID 98/14303‐3) and from Associação Fundo de Incentivo àPsicofarmacologia (AFIP).