REM Sleep Rebound as an Adaptive Response to Stressful Situations

Abstract

Stress and sleep are related to each other in a bidirectional way. If on one hand poor or inadequate sleep exacerbates emotional, behavioral, and stress-related responses, on the other hand acute stress induces sleep rebound, most likely as a way to cope with the adverse stimuli. Chronic, as opposed to acute, stress impairs sleep and has been claimed to be one of the triggering factors of emotional-related sleep disorders, such as insomnia, depressive- and anxiety-disorders. These outcomes are dependent on individual psychobiological characteristics, conferring even more complexity to the stress-sleep relationship. Its neurobiology has only recently begun to be explored, through animal models, which are also valuable for the development of potential therapeutic agents and preventive actions. This review seeks to present data on the effects of stress on sleep and the different approaches used to study this relationship as well as possible neurobiological underpinnings and mechanisms involved. The results of numerous studies in humans and animals indicate that increased sleep, especially the rapid eye movement phase, following a stressful situation is an important adaptive behavior for recovery. However, this endogenous advantage appears to be impaired in human beings and rodent strains that exhibit high levels of anxiety and anxiety-like behavior.

Keywords: HPA axis; REM sleep; animal models; anxiety-related behavior; prolactin; sleep; stress.

Figure 1

Schematic representation of the hypothalamic–pituitary–adrenal (HPA) axis and main effects of corticotropin releasing hormone (CRH) and glucocorticoids (GC). Filled arrows represent stimulatory effects, whereas dotted arrows represent inhibition. The main sites of GC negative feedback are the prefrontal cortex, hippocampus, hypothalamus, and pituitary.

Figure 2

Schematic representation the effects of stress on NREMS and REMS rebound. The longer the stress period the higher the corticosterone (CORT) secretion and as a consequence, there is a gradual inhibition of NREMS rebound. REMS, however, is regulated by optimum levels of CORT, so either very low or very high levels (induced by very short or very long periods of stress) result in meager rebound. Data is adapted from Marinesco et al. (1999).

Figure 3

The serotonergic hypothesis of acute stress-induced sleep rebound. According to this hypothesis, stress induces the release of serotonin, which is metabolized to 5-hydroxyindole substances that stimulates the cleavage of pro-opiomelanocortin, originating adrenocorticotropic hormone (ACTH), alpha-melanocyte stimulating hormone (α-MSH) and β-endorphin. ACTH is metabolized originating corticotropin-like intermediate lobe peptide (CLIP), which is a major inducer of REMS.

Figure 4

Working model of the prolactinergic hypothesis of stress-induced REMS rebound. Stressors (including REMS deprivation) increase serotonin release from the Raphe nuclei (1), which, in turn, could stimulate the release of PRL from the lateral hypothalamic area – LHA (2). Descending PRL projections from the LHA to the Raphe nuclei would close the self-stimulatory circuit, producing a further release of serotonin. In parallel, serotonergic projection to the arcuate nucleus – Arc (3) stimulates POMC cleavage resulting in production and secretion of CLIP in this region. Descending projections from the Arc to the Raphe nuclei would lead to accumulation of CLIP in this area, inhibiting serotonin secretion, thus releasing the cholinergic activity in pontine nuclei (4), leading to REMS. PRL would also produce excitation of pontine cholinergic neurons, contributing to the expression of REMS rebound.