RT Journal Article
SR Electronic
T1 Sleep Deprivation Decreases Binding of [<sup>11</sup>C]Raclopride to Dopamine D<sub>2</sub>/D<sub>3</sub> Receptors in the Human Brain
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8454
OP 8461
DO 10.1523/JNEUROSCI.1443-08.2008
VO 28
IS 34
A1 Volkow, Nora D.
A1 Wang, Gene-Jack
A1 Telang, Frank
A1 Fowler, Joanna S.
A1 Logan, Jean
A1 Wong, Christopher
A1 Ma, Jim
A1 Pradhan, Kith
A1 Tomasi, Dardo
A1 Thanos, Peter K.
A1 Ferré, Sergi
A1 Jayne, Millard
YR 2008
UL http://www.jneurosci.org/content/28/34/8454.abstract
AB 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.