title: Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain.
abstract: 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 A2A receptors (A2AR). 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 D2/D3 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 D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 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 D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors.
authors: Intramural Research Program, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors: N D
authors: ND
authors: Volkow
authors: Intramural Research Program, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors: G-J
authors: GJ
authors: Wang
authors: Brookhaven National Laboratory, Upton, NY, USA.
authors: J
authors: J
authors: Logan
authors: Brookhaven National Laboratory, Upton, NY, USA.
authors: D
authors: D
authors: Alexoff
authors: Brookhaven National Laboratory, Upton, NY, USA.
authors: J S
authors: JS
authors: Fowler
authors: Brookhaven National Laboratory, Upton, NY, USA.
authors: P K
authors: PK
authors: Thanos
authors: Intramural Research Program, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors: C
authors: C
authors: Wong
authors: Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
authors: V
authors: V
authors: Casado
authors: Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
authors: S
authors: S
authors: Ferre
authors: Intramural Research Program, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors: D
authors: D
authors: Tomasi
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D001143:Arousal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D049268:Positron-Emission Tomography; D011699:Putamen / Q000187:drug effects; D020891:Raclopride; D043705:Receptor, Adenosine A2A / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000187:drug effects* / Q000378:metabolism; D066328:Ventral Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; C581293:DRD2 protein, human; C493593:DRD3 protein, human; D018492:Dopamine Antagonists; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D002110:Caffeine; D020891:Raclopride; D004298:Dopamine