Cited by 312Neuroscience and Neuropharmacology ResearchStress Responses and CortisolNeurotransmitter Receptor Influence on Behavior

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Caffeine acts through neuronal adenosine A 2A receptors to prevent mood and memory dysfunction triggered by chronic stress

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Kaster, Manuella P., Machado, Nuno J., Silva, Henrique B., Nunes, Ana, Ardais, Ana Paula, Santana, Magda, Baqi, Younis, Müller, Christa E., Rodrigues, Ana Lúcia S., Porciúncula, Lisiane O., Chen, Jiang Fan, Tomé, Ângelo R., Agostinho, Paula, Canas, Paula M., Cunha, Rodrigo A.·2015·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1423088112PMC PMC4485143

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Abstract

Significance: Epidemiological studies show that individuals exposed to repeated stress, a major trigger of depression, increase their caffeine intake, which correlates inversely with the incidence of depression. However, the mechanism underlying this protective effect is unknown. We used an animal model of chronic unpredictable stress (CUS) to show that caffeine prevents the maladaptive changes caused by CUS in a manner mimicked by the selective blockade of adenosine A 2A receptors (A 2A R). CUS enhanced A 2A R in synapses, and the selective elimination of neuronal A 2A R abrogated CUS modifications. Moreover, A 2A R blockade also afforded a therapeutic benefit, paving the way to consider A 2A R blockers as a strategy to manage the negative impact of chronic stress on mood and memory.

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Authors: Kaster, M. P., Machado, N. J., Silva, H. B., Nunes, A., Ardais, A. P., Santana, M., Baqi, Y., Müller, C. E., Rodrigues, A. L. S., Porciúncula, L. O., Chen, J. F., Tomé, Â. R., Agostinho, P., Canas, P. M., & Cunha, R. A.
Affiliations: Universidade Federal de Santa Catarina (BR)
Centro de Neurociências e Biologia Celular (PT)
Universidade Federal do Rio Grande do Sul (BR)
University of Bonn (DE)
Boston University (US)
University of Coimbra (PT)
ORCID: Kaster, Manuella P.
Machado, Nuno J.
Silva, Henrique B.
Nunes, Ana
Ardais, Ana Paula
Santana, Magda
Baqi, Younis
Müller, Christa E.
Rodrigues, Ana Lúcia S.
Porciúncula, Lisiane O.
Chen, Jiang Fan
Tomé, Ângelo R.
Agostinho, Paula
Canas, Paula M.
Cunha, Rodrigo A.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2015-06-08
Volume: 112
Issue: 25
Pages: 7833-7838
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1423088112
PMC: PMC4485143
OpenAlex: W1591120748
Cited by: 312
References: 48
Citations by year: 2026: 24 · 2025: 28 · 2024: 23 · 2023: 26 · 2022: 33 · 2021: 36 · 2020: 26 · 2019: 29 · 2018: 41 · 2017: 19 · 2016: 17 · 2015: 10
FWCI: 13.53
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.pnas.org/site/misc/userlicense.xhtml (vor, 183 d)
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Brain and Behavior Research Foundation (2014 NARSAD INDEPENDENT INVESTIGATOR GRANT)
DOD | Defense Advanced Research Projects Agency (W911NF-10-1-0059)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: caffeine, adenosine A2A receptor, chronic unpredictable mild stress, depression, anxiety, memory impairment, hippocampus, synaptic plasticity, glutamatergic terminals, SNAP-25, syntaxin, VGLUT1, adenosine A2A receptor antagonists, neuroprotection
MeSH terms: Animals, Caffeine, Male, Memory Disorders, Mice, Inbred C57BL, Neurons, Stress, Psychological, Mood Disorders, Receptor, Adenosine A2A, Mice

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Caffeine acts through neuronal adenosine A 2A receptors to prevent mood and memory dysfunction triggered by chronic stress

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