The DOI matches its Crossref record; 128 of the 129 references it cites were found in a registry or an index.
An update on the mechanisms of the psychostimulant effects of caffeine
Open accessAbstract
There has been a long debate about the predominant involvement of the different adenosine receptor subtypes and the preferential role of pre‐ versus post‐synaptic mechanisms in the psychostimulant effects of the adenosine receptor antagonist caffeine. Both striatal A 1 and A 2A receptors are involved in the motor‐activating and probably reinforcing effects of caffeine, although they play a different role under conditions of acute or chronic caffeine administration. The present review emphasizes the key integrative role of adenosine and adenosine receptor heteromers in the computation of information at the level of the striatal spine module (SSM). This local module is mostly represented by the dendritic spine of the medium spiny neuron with its glutamatergic and dopaminergic synapses and astroglial processes that wrap the glutamatergic synapse. In the SSM, adenosine acts both pre‐ and post‐synaptically through multiple mechanisms, which depend on heteromerization of A 1 and A 2A receptors among themselves and with D 1 and D 2 receptors, respectively. A critical aspect of the mechanisms of the psychostimulant effects of caffeine is its ability to release the pre‐ and post‐synaptic brakes that adenosine imposes on dopaminergic neurotransmission by acting on different adenosine receptor heteromers localized in different elements of the SSM.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In addition, functional interactions between A2A receptors and dopaminergic signaling pathways suggest that caffeine’s central stimulant effects likely arise from the broader disinhibition of a multi-neurotransmitter network, driven by concurrent antagonism of A1 and A2A receptors, rather than from blockade of a single receptor pathway alone [37,38].”
From Pre-Exercise Caffeine as a Modulator of Exercise-Induced Acute Cardiometabolic Responses: A Narrative Review (2026) · cites this paper as [37]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In addition, high concentrations of caffeine inhibit phosphodiesterase activity 3 and stimulate dopamine D2 receptors.9”
From Theanine maintains sleep quality in healthy young women by suppressing the increase in caffeine-induced wakefulness after sleep onset (2023) · cites this paper as [9]
Experimental — accuracy not yet measuredIn the citing paper
“Furthermore, caffeine excites neural circuits that project from the basal ganglia to the striatum and cerebral cortex.9”
From Theanine maintains sleep quality in healthy young women by suppressing the increase in caffeine-induced wakefulness after sleep onset (2023) · cites this paper as [9]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Dopamine, learning and motivation.
Wise, R. A. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1406 · Cited by 3,379
Fredholm, B. B., Bättig, K., Holmén, J., Nehlig, A., & Zvartau, E. E. (1999) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01396-6 · Cited by 2,624
International Union of Pharmacology. XXV. Nomenclature and Classification of Adenosine Receptors
Fredholm, B. B., IJzerman, A. P., Jacobson, K. A., Klotz, K.-N., & Linden, J. (2001) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01511-4 · Cited by 2,585
Ungerstedt, U. (1971) · Acta Physiologica Scandinavica · doi:10.1111/j.1365-201x.1971.tb11000.x · Cited by 1,920
Ikemoto, S. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.05.004 · Cited by 1,477
Astrocytic Purinergic Signaling Coordinates Synaptic Networks
Pascual, O., Casper, K. B., Kubera, C., Zhang, J., Revilla-Sanchez, R., Sul, J.-Y., Takano, H., Moss, S. J., McCarthy, K., & Haydon, P. G. (2005) · Science · doi:10.1126/science.1116916 · Cited by 1,280
Mechanisms of neurotransmitter release by amphetamines: A review
Sulzer, D., Sonders, M. S., Poulsen, N. W., & Galli, A. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.04.003 · Cited by 1,243
Plasma membrane monoamine transporters: structure, regulation and function
Torres, G. E., Gainetdinov, R. R., & Caron, M. G. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1008 · Cited by 936
Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor
Ledent, C. A., Vaugeois, J., Schiffmann, S. N., Pedrazzini, T., Yacoubi, M. E., Vanderhaeghen, J. J., Costentin, J., Heath, J. K., Vassart, G., & Parmentier, M. (1997) · Nature · doi:10.1038/41771 · Cited by 918
Adenosine–dopamine receptor–receptor interactions as an integrative mechanism in the basal ganglia
Ferré, S., Fuxé, K., Fredholm, B. B., Morelli, M., & Popoli, P. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(97)01096-5 · Cited by 825
Self-citation
Research works printed but not linked: 1
- Rall T. W., 1982, Evolution of the mechanism of action of methylxanthines from calcium mobilizers to antagonists of adenosine receptors, Pharmacologist, 24, 277
Cited by
Sorted by citations
The 2.6 Angstrom Crystal Structure of a Human A 2A Adenosine Receptor Bound to an Antagonist
Jaakola, V., Griffith, M. T., Hanson, M. A., Cherezov, V., Chien, E. Y. T., Lane, J. R., IJzerman, A. P., & Stevens, R. C. (2008) · Science · doi:10.1126/science.1164772 · Cited by 1,786
Heckman, M. A., Weil, J., & de Mejía, E. G. (2010) · Journal of Food Science · doi:10.1111/j.1750-3841.2010.01561.x · Cited by 1,116
“The blockage of adenosine to the neurons causes the sleep promoting effects of adenosine to stop, resulting in the neurons speeding up instead of slowing down (Ferre 2008).”
BackgroundKennedy, D. O., & Wightman, E. L. (2011) · Advances in Nutrition · doi:10.3945/an.110.000117 · Cited by 684
“Similarly, in mammals, caffeine is a competitive antagonist of inhibitory adenosine A1 and A2 receptors, which in turn leads to activation via increased dopaminergic and glutamatergic activity (64).”
BackgroundInterindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption
Nehlig, A. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014407 · Cited by 632
Scientific Opinion on the safety of caffeine
EFSA Panel on Dietetic Products, N. A. A. (. (2015) · EFSA Journal · doi:10.2903/j.efsa.2015.4102 · Cited by 613
“Prolonged administration of an adenosine A2A receptor antagonist does not induce tolerance to its motor stimulant effect, suggesting that caffeine tolerance may be dependent on blockade of A1, rather than A2A, receptors (Ferre, 2008).”
Background
Metadata
- Authors
- Ferré, S.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Ferré, Sergi
- ORCID
- Ferré, Sergi
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-12-18
- Volume
- 105
- Issue
- 4
- Pages
- 1067-1079
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1994970739
- Cited by
- 440
- References
- 129
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 14 · 2023: 23 · 2022: 31 · 2021: 30 · 2020: 15 · 2019: 26 · 2018: 24 · 2017: 18 · 2016: 32 · 2015: 32 · 2014: 25 · 2013: 34 · 2012: 29
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- caffeine, psychostimulant effects, adenosine receptors, adenosine A1 receptor, adenosine A2A receptor, receptor heteromers, dopamine signaling, glutamatergic synapses, dopamine D1 receptor, dopamine D2 receptor, motor activation, reinforcement, adenosine
- MeSH terms
- Adenosine, Central Nervous System Stimulants, Animals, Caffeine, Humans, Receptors, Purinergic P1, Purinergic P1 Receptor Agonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
