Evidence that sleep deprivation downregulates dopamine D2R in ventral striatum in the human brain
Open accessAbstract
Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [(11)C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([(11)C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [(11)C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.
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Sleep deprivation reduces dopamine D2/D3 receptors in the ventral striatum without affecting basal dopamine release.
“sleep deprivation reduces dopamine D2/D3 receptors in the VS without affecting basal dopamine release (96)”
From Impact of Sleep and Circadian Rhythms on Addiction Vulnerability in Adolescents (2018) · cites this paper as [96]
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- Authors
- Volkow, N. D., Tomasi, D., Wang, G.-J., Telang, F., Fowler, J. S., Logan, J., Benveniste, H., Kim, R., Thanos, P. K., & Ferré, S.
- Affiliations
- National Institute on Drug Abuse (US)
- Brookhaven National Laboratory (US)
- National Institute on Alcohol Abuse and Alcoholism (US)
- Stony Brook University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-05-09
- Volume
- 32
- Issue
- 19
- Pages
- 6711-6717
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3433285
- OpenAlex
- W2020672544
- Cited by
- 254
- References
- 59
- Citations by year
- 2026: 17 · 2025: 22 · 2024: 18 · 2023: 24 · 2022: 24 · 2021: 21 · 2020: 24 · 2019: 19 · 2018: 17 · 2017: 18 · 2016: 10 · 2015: 13 · 2014: 9 · 2013: 12 · 2012: 5
- FWCI
- 6.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Energy (76CH00016, DE-AC01-76CH00016)
- National Institutes of Health (DE-AC01-76CH00016)
- National Institute on Alcohol Abuse and Alcoholism (ZIAAA000550)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- sleep deprivation, dopamine D2/D3 receptors, receptor down-regulation, ventral striatum, methylphenidate, wakefulness, alertness, sleepiness, REM sleep deprivation, microdialysis, dopamine release
- MeSH terms
- Adult, Animals, Basal Ganglia, Brain, Humans, Male, Sleep Deprivation, Wakefulness, Down-Regulation, Rats, Sprague-Dawley, Receptors, Dopamine D2, Receptors, Dopamine D3, Rats, Young Adult, Dopamine D2 Receptor Antagonists
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