TY - JOUR 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. SP - 8454 LP - 8461 DO - 10.1523/JNEUROSCI.1443-08.2008 VL - 28 IS - 34 AU - Nora D. Volkow AU - Gene-Jack Wang AU - Frank Telang AU - Joanna S. Fowler AU - Jean Logan AU - Christopher Wong AU - Jim Ma AU - Kith Pradhan AU - Dardo Tomasi AU - Peter K. Thanos AU - Sergi Ferré AU - Millard Jayne Y1 - 2008/08/20 UR - http://www.jneurosci.org/content/28/34/8454.abstract N2 - 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. ER -