Caffeine increases striatal dopamine D2/D3 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 ...
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The findings from these two studies thus suggest that caffeine at doses typically consumed by humans might enhance DA signaling by increasing D2/D3R levels or their affinity rather than by increasing DA release in the striatum.
Here we interpret our results of increases in BPND (in BPND availability) with caffeine to suggest that they reflect increases in D2/D3R levels rather than reflecting decreases in endogenous DA
Our results indicate that in humans, caffeine at the doses typically consumed, does not increase DA in the striatum.
This is consistent with findings from microdialysis studies in rodent showing that caffeine (0.25–5 mg kg−1 intravenously or 1.5 to 30 mg kg−1 intraperitoneally) did not increase DA in the nucleus accumbens,22, 23 though a study reported increases with a large (10 mg kg−1 intraperitoneally) but not a lower caffeine dose (3 mg kg−1 intraperitoneally).21 Thus, on the basis of the current and prior findings24 and the preclinical results, caffeine at doses that are relevant to human consumption does not appear to increase DA in the nucleus accumbens.
As the ability of drugs of abuse to increase DA is necessary for their rewarding effects and for the neuroadaptations associated with the addiction phenotype,49 this could explain why caffeine does not produce the compulsive administration and the loss of control that characterizes addiction.50
Caffeine-induced increases in D2/D3R in VS were associated with increases in alertness. This association between alertness and D2/D3R replicates our previous findings with sleep deprivation but in the opposite direction, in which we showed that the decreases in D2/D3R availability in VS with sleep deprivation were associated with reductions in alertness.5 In the prior PET study, caffeine-induced increases in striatal D2/D3R availability were associated with reduced tiredness.24
Thus this provides evidence that enhanced signaling through D2/D3R in striatal regions might enhance alertness or decrease tiredness, whereas reduced signaling might decrease alertness or increase fatigue.
