TY - JOUR
T1 - Evidence that sleep deprivation down regulates dopamine D2R in ventral striatum in the human brain
AU - Volkow, Nora D.
AU - Tomasi, Dardo
AU - Wang, Gene Jack
AU - Telang, Frank
AU - Fowler, Joanna S.
AU - Logan, Jean
AU - Benveniste, Helene
AU - Kim, Ron
AU - Thanos, Panayotis K.
AU - Ferré, Sergi
PY - 2012/5/9
Y1 - 2012/5/9
N2 - Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [ 11C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([ 11C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor down regulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [ 11C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a down regulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.
AB - Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [ 11C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([ 11C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor down regulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [ 11C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a down regulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.
UR - http://www.scopus.com/inward/record.url?scp=84860672209&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0045-12.2012
DO - 10.1523/JNEUROSCI.0045-12.2012
M3 - Article
C2 - 22573693
AN - SCOPUS:84860672209
SN - 0270-6474
VL - 32
SP - 6711
EP - 6717
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 19
ER -