Sleep deprivation decreases binding of [11C]raclopride to dopamine D2/D3 receptors in the human brain.
Sleep deprivation did not affect dopamine transporters (target for most wake-promoting medications) and thus dopamine increases are likely to reflect increases in dopamine cell firing and/or release rather than decreases in dopamine reuptake. Because dopamine-enhancing drugs increase wakefulness, we postulate that dopamine increases after sleep deprivation is a mechanism by which the brain maintains arousal as the drive to sleep increases but one that is insufficient to counteract behavioral and cognitive impairment. Sleep deprivation can markedly impair human performance contributing to accidents and poor productivity. The mechanisms underlying this impairment are not well understood, but brain dopamine systems have been implicated. Here, we test whether one night of sleep deprivation changes dopamine brain activity. We studied 15 healthy subjects using positron emission tomography and [11C]raclopride (dopamine D2/D3 receptor radioligand) and [11C]cocaine (dopamine transporter radioligand). Subjects were tested twice: after one night of rested sleep and after one night of sleep deprivation. The specific binding of [11C]raclopride in the striatum and thalamus were significantly reduced after sleep deprivation and the magnitude of this reduction correlated with increases in fatigue (tiredness and sleepiness) and with deterioration in cognitive performance (visual attention and working memory). In contrast, sleep deprivation did not affect the specific binding of [11C]cocaine in the striatum. Because [11C]raclopride competes with endogenous dopamine for binding to D2/D3 receptors, we interpret the decreases in binding to reflect dopamine increases with sleep deprivation. However, we cannot rule out the possibility that decreased [11C]raclopride binding reflects decreases in receptor levels or affinity. Sleep deprivation did not affect dopamine transporters (target for most wake-promoting medications) and thus dopamine increases are likely to reflect increases in dopamine cell firing and/or release rather than decreases in dopamine reuptake. Because dopamine-enhancing drugs increase wakefulness, we postulate that dopamine increases after sleep deprivation is a mechanism by which the brain maintains arousal as the drive to sleep increases but one that is insufficient to counteract behavioral and cognitive impairment.
Volkow
Nora D
ND
National Institute on Drug Abuse, Bethesda, Maryland 20892, USA. nvolkow@nida.nih.gov
Wang
Gene-Jack
GJ
Telang
Frank
F
Fowler
Joanna S
JS
Logan
Jean
J
Wong
Christopher
C
Ma
Jim
J
Pradhan
Kith
K
Tomasi
Dardo
D
Thanos
Peter K
PK
Ferré
Sergi
S
Jayne
Millard
M
D000328:Adult; D001143:Arousal; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003042:Cocaine / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism; D005221:Fatigue / Q000209:etiology; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D020891:Raclopride / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012892:Sleep Deprivation / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D013788:Thalamus / Q000378:metabolism
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D020891:Raclopride; D003042:Cocaine; D004298:Dopamine