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Caffeine increases striatal dopamine D(2)/D(3) receptor availability in the human brain
Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A(2A...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462609/ https://www.ncbi.nlm.nih.gov/pubmed/25871974 http://dx.doi.org/10.1038/tp.2015.46 |
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author | Volkow, N D Wang, G-J Logan, J Alexoff, D Fowler, J S Thanos, P K Wong, C Casado, V Ferre, S Tomasi, D |
author_facet | Volkow, N D Wang, G-J Logan, J Alexoff, D Fowler, J S Thanos, P K Wong, C Casado, V Ferre, S Tomasi, D |
author_sort | Volkow, N D |
collection | PubMed |
description | Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A(2A) receptors (A(2A)R). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [(11)C]raclopride (DA D(2)/D(3) receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D(2)/D(3) receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D(2)/D(3) receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D(2)/D(3) receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D(2)/D(3) receptor availability. Instead, we interpret our findings to reflect an increase in D(2)/D(3) receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D(2)/D(3) receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D(2)/D(3) receptors. |
format | Online Article Text |
id | pubmed-4462609 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44626092015-06-11 Caffeine increases striatal dopamine D(2)/D(3) receptor availability in the human brain Volkow, N D Wang, G-J Logan, J Alexoff, D Fowler, J S Thanos, P K Wong, C Casado, V Ferre, S Tomasi, D Transl Psychiatry Original Article Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A(2A) receptors (A(2A)R). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [(11)C]raclopride (DA D(2)/D(3) receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D(2)/D(3) receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D(2)/D(3) receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D(2)/D(3) receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D(2)/D(3) receptor availability. Instead, we interpret our findings to reflect an increase in D(2)/D(3) receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D(2)/D(3) receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D(2)/D(3) receptors. Nature Publishing Group 2015-04 2015-04-14 /pmc/articles/PMC4462609/ /pubmed/25871974 http://dx.doi.org/10.1038/tp.2015.46 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Volkow, N D Wang, G-J Logan, J Alexoff, D Fowler, J S Thanos, P K Wong, C Casado, V Ferre, S Tomasi, D Caffeine increases striatal dopamine D(2)/D(3) receptor availability in the human brain |
title | Caffeine increases striatal dopamine D(2)/D(3) receptor availability in the human brain |
title_full | Caffeine increases striatal dopamine D(2)/D(3) receptor availability in the human brain |
title_fullStr | Caffeine increases striatal dopamine D(2)/D(3) receptor availability in the human brain |
title_full_unstemmed | Caffeine increases striatal dopamine D(2)/D(3) receptor availability in the human brain |
title_short | Caffeine increases striatal dopamine D(2)/D(3) receptor availability in the human brain |
title_sort | caffeine increases striatal dopamine d(2)/d(3) receptor availability in the human brain |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462609/ https://www.ncbi.nlm.nih.gov/pubmed/25871974 http://dx.doi.org/10.1038/tp.2015.46 |
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