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.
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“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]
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“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]
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“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]
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“1,44 By blocking adenosine receptors, caffeine inhibits the vasodilation typically maintained by endogenous adenosine, thereby promoting vasoconstriction within the highly vascularized choroidal tissue.”
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KAFEİNİN PSİKOFARMAKOLOJİK ETKİLERİ: NÖROPROTEKTİF KULLANIMA İLİŞKİN ÇIKARIMLAR
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“In the central nervous system, caffeine stimulates dopaminergic and glutamatergic activity by antagonizing inhibitory adenosine A1 and A2 receptors (Ferré, 2008).”
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
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