Timing is everything: does the robust upregulation of noradrenergically regulated plasticity genes underlie the rapid antidepressant effects of sleep deprivation?
Abstract
The mechanisms by which sleep deprivation brings about rapid antidepressant effects remain to be elucidated. Biological rhythms have the capacity to temporally dissociate biochemical processes, and imposing a temporal coincidence on normally dissociated events can have striking and unexpected effects. In this context, it is noteworthy that the locus coeruleus (LC) noradrenergic projection is quiescent only during rapid-eye-movement (REM) sleep, when the target tissues display their greatest sensitivity; indeed, the temporal dissociation between the firing of the LC noradrenergic neurons and the sensitivity of its postsynaptic targets in the cortex may have considerable relevance for the antidepressant effects of sleep deprivation. Sleep deprivation rapidly upregulates several plasticity-related genes, effects that are noradrenergically mediated; these are the very same genes that are upregulated by chronic antidepressants. Thus, activating the norepinephrine system during REM sleep (by infusing an alpha(2) antagonist) may allow an interaction with a primed, sensitized postsynaptic milieu, thereby rapidly increasing the expression of plasticity genes and consequently a rapid antidepressant response.
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The relationship of LTP during waking to increased production of slow waves in sleep is likely relevant for depression, in that most effective antidepressants increase expression of plasticity-related genes much like sleep deprivation, although on a longer time course.
“The relationship of LTP during waking to increased production of slow waves in sleep is likely relevant for depression, in that most effective antidepressants increase expression of plasticity-related genes (reviewed in Duman, 2002; Payne et al., 2002) much like sleep deprivation (Cirelli et al., 2004), although on a longer time course.”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Payne et al., 2002
Cites
Psychopharmacology: The Fourth Generation of Progress
Bloom, F. E., & Kupfer, D. J. (1995) · Medical Entomology and Zoology · Cited by 2,985 · see citing works
Davenport, Y. B., Adland, M. L., Gold, P. W., & Goodwin, F. K. (1984) · The Lancet · doi:10.1016/s0140-6736(84)92810-1 · Cited by 2,925 · see citing works
Papageorgis, D. (1991) · Behaviour Research and Therapy · doi:10.1016/0005-7967(91)90087-j · Cited by 1,542 · see citing works
Antidepressant-like effect of brain-derived neurotrophic factor (BDNF)
Siuciak, J. A., Lewis, D. R., Wiegand, S. J., & Lindsay, R. M. (1997) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(96)00169-4 · Cited by 841 · see citing works
Wu, J. C., & Bunney, W. E. (1990) · American Journal of Psychiatry · doi:10.1176/ajp.147.1.14 · Cited by 614 · see citing works
Preclinical models: status of basic research in depression
Nestler, E. J., Gould, E., & Manji, H. K. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01405-1 · Cited by 559 · see citing works
Self-citationManji, H. K., Quiroz, J. A., Sporn, J., Payne, J. L., Denicoff, K. D., Gray, N. A., Zarate, C. A., & Charney, D. S. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00117-3 · Cited by 499 · see citing works
Self-citationInitiation and adaptation: a paradigm for understanding psychotropic drug action
(1996) · American Journal of Psychiatry · doi:10.1176/ajp.153.2.151 · Cited by 490 · see citing works
Sleep deprivation in depression: what do we know, where do we go?
Wirz-Justice, A., & Van den Hoofdakker, R. H. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00125-0 · Cited by 429 · see citing works
Cirelli, C., & Tononi, G. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-24-09187.2000 · Cited by 369 · see citing works
Cirelli, C., & Tononi, G. (2000) · Brain Research · doi:10.1016/s0006-8993(00)03008-0 · Cited by 365 · see citing works
Synaptic plasticity and mood disorders
Duman, R. S. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001016 · Cited by 363 · see citing works
Manji, H. K., Duman, R. S., Duman, F. A. R. S., & PhD (2025) · Psychopharmacology Bulletin · doi:10.64719/pb.4260 · Cited by 330 · see citing works
Self-citationMolecular machines integrate coincident synaptic signals
Bourne, H. R., & Nicoll, R. A. (1993) · Cell · doi:10.1016/s0092-8674(05)80029-7 · Cited by 311 · see citing works
Delayed pharmacological effects of antidepressants
Frazer, A., & Benmansour, S. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001015 · Cited by 160 · see citing works
A function for REM sleep: regulation of noradrenergic receptor sensitivity.
Siegel, J. M., & Rogawski, M. A. (1988) · Brain Research · doi:10.1016/0165-0173(88)90007-0 · Cited by 151 · see citing works
BIOLOGICAL TIMING AND THE CLOCK METAPHOR: OSCILLATORY AND HOURGLASS MECHANISMS
Rensing, L., Meyer, U., & Ruoff, P. (2001) · Chronobiology International · doi:10.1081/cbi-100103961 · Cited by 121 · see citing works
Ikonomov, O. C., & Manji, H. K. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.10.1506 · Cited by 94 · see citing works
Self-citationSleep deprivation: Effects on circadian rhythms of rat brain neurotransmitter receptors
Wirz‐Justice, A., Tobler, I., Kafka, M. S., Naber, D., Marangos, P. J., Borbély, A. A., & Wehr, T. A. (1981) · Psychiatry Research · doi:10.1016/0165-1781(81)90062-7 · Cited by 72 · see citing works
Neumeister, A., Praschak-Rieder, N., Heßelmann, B., Vitouch, O., Rauh, M., Barocka, A., Tauscher, J. T., & Kasper, S. F. (1998) · Archives of General Psychiatry · doi:10.1001/archpsyc.55.2.167 · Cited by 66 · see citing works
Response of the Norepinephrine System to Antidepressant Drugs
Szabo, S. T., & Blier, P. (2001) · CNS Spectrums · doi:10.1017/s1092852900001371 · Cited by 26 · see citing works
Troncone, L. R. P., Braz, S., Benedito, M. A. C., & Tufik, S. (1986) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(86)90257-1 · Cited by 23 · see citing works
Potential mechanisms of the sleep therapies for depression
Ringel, B. L., & Szuba, M. P. (2001) · Depression and Anxiety · doi:10.1002/da.1044 · Cited by 16 · see citing works
Smolensky, M. H. (2006) · CNS Spectrums · doi:10.1017/s1092852900008026 · Cited by 11 · see citing works
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McEwen, B. S. (2007) · Physiological Reviews · doi:10.1152/physrev.00041.2006 · Cited by 4,981 · see citing works
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Tononi, G., & Cirelli, C. (2006) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2005.05.002 · Cited by 2,151 · see citing works
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Sanacora, G., Zarate, C. A., Krystal, J. H., & Manji, H. K. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2462 · Cited by 894 · see citing works
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Machado-Vieira, R., Baumann, J., Wheeler-Castillo, C., Latov, D., Henter, I. D., Salvadore, G., & Zarate, C. A. (2010) · Pharmaceuticals · doi:10.3390/ph3010019 · Cited by 263 · see citing works
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- Authors
- Payne, J. L., Quiroz, J. A., Zarate, C. A., & Manji, H. K.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Payne, Jennifer L
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 52
- Issue
- 10
- Pages
- 921-926
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2025341479
- Cited by
- 46
- References
- 24
- Citations by year
- 2022: 1 · 2021: 2 · 2019: 3 · 2016: 1 · 2014: 2 · 2013: 1 · 2012: 4
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- sleep deprivation, rapid antidepressant effects, noradrenergic system, locus coeruleus, REM sleep, biological rhythms, temporal coincidence, alpha2-adrenoceptor antagonists
- MeSH terms
- Antidepressive Agents, Gene Expression Regulation, Humans, Locus Coeruleus, Neuronal Plasticity, Norepinephrine, Sleep Deprivation, Sleep, REM, Drug Design, Up-Regulation
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