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Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain - PubMed

  • ️Thu Jan 01 2015

Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain

N D Volkow et al. Transl Psychiatry. 2015.

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.

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Figures

Figure 1
Figure 1

Behavioral effects of placebo and caffeine before and 30 and 120 min after their administration. Significance corresponds to comparison between placebo (gray symbols) and caffeine (black symbols) and values correspond to means and standard errors.

Figure 2
Figure 2

(a) Brain maps obtained with Statistical Parametric Mapping (SPM) showing significant differences in D2/D3R availability, which was quantified as nondisplaceable binding potential (BPND), between placebo and caffeine for the contrast caffeine >placebo. Threshold for significance corresponds to Pu<0.01, clusters >100 voxels. (b) Individual values for BPND from measures extracted in dorsal putamen and in ventral striatum after placebo and after caffeine.

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