Chronically restricted sleep leads to depression-like changes in neurotransmitter receptor sensitivity and neuroendocrine stress reactivity in rats

Abstract

Study Objectives: Frequently disrupted and restricted sleep is a common problem for many people in our Western society. In the long run, insufficient sleep may have repercussions for health and may sensitize individuals to psychiatric diseases. In this context, we applied an animal model of chronic sleep restriction to study effects of sleep loss on neurobiological and neuroendocrine systems that have been implied in the pathophysiology of depression, particularly the serotonergic system and the hypothalamic-pituitary- adrenal (HPA) axis. Design: Adult rats were exposed to a schedule of chronic partial sleep deprivation allowing them only 4 h of sleep per day. Sleep restriction was achieved by placing the animals in slowly rotating drums. To examine the regulation and reactivity of the HPA axis, blood samples were collected to measure adrenocorticotropin (ACTH) and corticosterone (CORT) responses. Measurements and Results: While one day of restricted sleep had no significant effect on HPA axis stress reactivity, sleep restriction for a week caused a blunted pituitary ACTH response in a conditioned fear paradigm. Despite this lower ACTH response, adrenal CORT release was normal. The blunted pituitary response may be related to reduced sensitivity of serotonin-1A receptors and/or receptors for corticotropin-releasing hormone (CRH), since sleep restricted rats showed similar reductions in ACTH release to direct pharmacological stimulation with a serotonin-1A agonist or CRH. Conclusions: Chronic sleep restriction may lead to changes in neurotransmitter receptor systems and neuroendocrine reactivity in a manner similar to that seen in depression. This experimental study thus supports the hypothesis that disrupted and restricted sleep may contribute to the symptomatology of psychiatric disorders.