Arousal Effect of Caffeine Depends on Adenosine A2A Receptors in the Shell of the Nucleus Accumbens
Open accessAbstract
Caffeine, the most widely used psychoactive compound, is an adenosine receptor antagonist. It promotes wakefulness by blocking adenosine A(2A) receptors (A(2A)Rs) in the brain, but the specific neurons on which caffeine acts to produce arousal have not been identified. Using selective gene deletion strategies based on the Cre/loxP technology in mice and focal RNA interference to silence the expression of A(2A)Rs in rats by local infection with adeno-associated virus carrying short-hairpin RNA, we report that the A(2A)Rs in the shell region of the nucleus accumbens (NAc) are responsible for the effect of caffeine on wakefulness. Caffeine-induced arousal was not affected in rats when A(2A)Rs were focally removed from the NAc core or other A(2A)R-positive areas of the basal ganglia. Our observations suggest that caffeine promotes arousal by activating pathways that traditionally have been associated with motivational and motor responses in the brain.
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Creatine supplementation acts on the fluid level of skeletal muscle cells, as demonstrated by a double-blind, controlled study with 0.3 g/kg BW creatine for 7 days in 13 soccer players, promoting ATP resynthesis and subsequent improvements in soccer players' performance.
“In addition, creatine supplementation acts on the fluid level of skeletal muscle cells, as demonstrated by a double-blind, controlled work with 0.3 g kg -1 of body weight (BW) of creatine supplementation during 7 days involving 13 soccer players [9] promoting ATP resynthesis and subsequent improvements in the performance of soccer players.”
From Dietary and Ergogenic Supplementation to Improve Elite Soccer Players’ Performance (2021) · cites this paper as [9]
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Cites
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“Regardless of the source, the worldwide average caffeine consumption has been estimated to be just under 80 mg/d, although the levels of intake in countries such as Sweden and Finland are in the range of 400 mg of caffeine per day (Fredholm et al., 1999).”
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Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine
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Retracted
- Authors
- Lazarus, M., Shen, H.-Y., Cherasse, Y., Qu, W.-M., Huang, Z.-L., Bass, C. E., Winsky-Sommerer, R., Semba, K., Fredholm, B. B., Boison, D., Hayaishi, O., Urade, Y., & Chen, J.-F.
- Affiliations
- Boston University (US)
- Shanghai Medical College of Fudan University (CN)
- Wake Forest University Health Sciences (US)
- Dalhousie University (CA)
- Karolinska Institutet (SE)
- Legacy Health (US)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-07-06
- Volume
- 31
- Issue
- 27
- Pages
- 10067-10075
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3153505
- OpenAlex
- W2152851519
- Cited by
- 327
- References
- 5
- Citations by year
- 2026: 17 · 2025: 23 · 2024: 20 · 2023: 21 · 2022: 21 · 2021: 21 · 2020: 18 · 2019: 17 · 2018: 25 · 2017: 34 · 2016: 23 · 2015: 17 · 2014: 21 · 2013: 25 · 2012: 20
- FWCI
- 9.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- U.S. Department of Defense (W81XWH)
- Takeda Science Foundation
- Takeda Pharmaceutical Company
- National Natural Science Foundation of China (2011CB711000, 30821002)
- Ministry of Health, Labour and Welfare
- Ono Pharmaceutical
- National Institutes of Health (W81XWH, MH083973)
- Japan Society for the Promotion of Science (21300133, 21380081, 21500313)
- Japan Science and Technology Agency
- Shanghai Leading Academic Discipline Project
- National Institute of Mental Health (R01MH083973, MH083973)
- National Institute on Drug Abuse (DA019362, DA024763, K01DA024763, R01DA019362)
- National Institute of Neurological Disorders and Stroke (NS048995, R01NS048995, R01NS037403)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Pharmacology › Coffee research and impacts
- Keywords
- caffeine, adenosine A2A receptor, nucleus accumbens shell, arousal, wakefulness, adenosine receptor antagonism, basal ganglia, gene deletion, RNA interference, adeno-associated virus, motivational behavior
- MeSH terms
- Central Nervous System Stimulants, Analysis of Variance, Animals, Arousal, Basal Ganglia, Caffeine, Cell Line, Transformed, Choline O-Acetyltransferase, Dose-Response Relationship, Drug, Electroencephalography, Electromyography, Humans, Locomotion, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Nucleus Accumbens, Phosphopyruvate Hydratase, Transfection, Mutagenesis, Rats, Sprague-Dawley, Receptors, Dopamine D2, Mice, Knockout, RNA, Small Interfering, Receptor, Adenosine A2A, Green Fluorescent Proteins, Mice, Rats
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