Chronically restricted sleep leads to depression-like changes in neurotransmitter receptor sensitivity and neuroendocrine stress reactivity in rats
Open accessAbstract
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.
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Animal studies point towards a direct stimulatory effect of sleep loss on the HPA axis.
“Animal studies, however, have pointed towards a direct stimulatory effect of sleep loss on the HPA axis.[23][24][25]”
From Effects of Insufficient Sleep on Pituitary–Adrenocortical Response to CRH Stimulation in Healthy Men (2017) · cites this paper as [25]
The Abstract reports that one day of restricted sleep had no significant effect on HPA-axis stress reactivity, while a week of restriction blunted the pituitary ACTH response. The Discussion likewise reports reduced ACTH responses and unchanged or mildly reduced corticosterone responses, rather than a direct stimulatory effect. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredStudies in rodents have demonstrated that recurrent sleep restriction affects spontaneous pituitary-adrenal activity and the response to CRH and to experimental stressors.
“Studies in rodents have demonstrated that recurrent sleep restriction affects not only spontaneous pituitary-adrenal activity but also the response to corticotropin-releasing hormone (CRH) 25 and to experimental stressors.[23][24][25]”
From Effects of Insufficient Sleep on Pituitary–Adrenocortical Response to CRH Stimulation in Healthy Men (2017) · cites this paper as [25]
The Results (CRH Challenge) report a reduced ACTH response to injected CRH in sleep-restricted rats, and the Results and Discussion report a blunted ACTH response to conditioned fear. These passages support the claims about responses to CRH and experimental stressors, but our copy does not establish an effect on spontaneous pituitary-adrenal activity. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA study in rats reported a blunted ACTH response to CRH injection after recurrent partial sleep loss.
“Our results are in line with a study in rats that reported a blunted ACTH response to CRH injection after recurrent partial sleep loss.25”
From Effects of Insufficient Sleep on Pituitary–Adrenocortical Response to CRH Stimulation in Healthy Men (2017) · cites this paper as [25]
Sleep loss can affect neural systems involved in mood and behavior as well as in the regulation of circadian rhythms.
“they suggest that sleep loss can affect neural systems involved in mood and behavior as well as in the regulation of circadian rhythms (Novati et al., 2008).”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Novati et al., 2008
In rodents, chronic sleep restriction results in decreased sensitivity of 5HT1A receptors.
“In rodents, chronic sleep restriction results in decreased sensitivity of 5HT1A receptors, and although these experiments were conducted in adult animals, they suggest that sleep loss can affect neural systems involved in mood and behavior as well as in the regulation of circadian rhythms (Novati et al., 2008).”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Novati et al., 2008
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- Authors
- Novati, A., Roman, V., Cetin, T., Hagewoud, R., den Boer, J. A., Luiten, P. G. M., & Meerlo, P.
- Affiliations
- University of Groningen (NL)
- Corresponding author
- Meerlo, Peter
- ORCID
- Meerlo, Peter
- Venue
- SLEEP
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-11
- Volume
- 31
- Issue
- 11
- Pages
- 1579-1585
- ISSN
- 0161-8105 (ISSN-L)
- 1550-9109
- PMC
- PMC2579986
- OpenAlex
- W2137541886
- Cited by
- 204
- References
- 45
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 13 · 2023: 13 · 2022: 11 · 2021: 12 · 2020: 8 · 2019: 15 · 2018: 7 · 2017: 14 · 2016: 11 · 2015: 9 · 2014: 8 · 2013: 16 · 2012: 15
- FWCI
- 5.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- SLEEP (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- chronic sleep restriction, sleep deprivation, depression, 5-HT1A receptor, corticotropin-releasing factor, hypothalamic-pituitary-adrenal axis, ACTH response, corticosterone, fear conditioning, animal models of depression
- MeSH terms
- Animals, Conditioning, Psychological, Corticosterone, Corticotropin-Releasing Hormone, Depression, Fear, Hypothalamo-Hypophyseal System, Sleep Initiation and Maintenance Disorders, Male, Pituitary-Adrenal System, Sleep Deprivation, Stress, Psychological, Rats, Wistar, Receptors, Corticotropin, Receptor, Serotonin, 5-HT1A, Rats
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