Cited by 440Adenosine and Purinergic SignalingNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

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An update on the mechanisms of the psychostimulant effects of caffeine

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Ferré, Sergi·2008·Journal of Neurochemistry

DOI 10.1111/j.1471-4159.2007.05196.x

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Abstract

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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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
DOI: 10.1111/j.1471-4159.2007.05196.x
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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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An update on the mechanisms of the psychostimulant effects of caffeine

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