Hyperstimulation of striatal D2 receptors with sleep deprivation: Implications for cognitive impairment.
Sleep deprivation interferes with cognitive performance but the mechanisms are poorly understood. We recently reported that one night of sleep deprivation increased dopamine in striatum (measured with [(11)C]raclopride, a PET radiotracer that competes with endogenous dopamine for binding to D2 receptors) and that these increases were associated with impaired performance in a visual attention task. To better understand this association here we evaluate the relationship between changes in striatal dopamine (measured as changes in D2 receptor availability using PET and [(11)C]raclopride) and changes in brain activation to a visual attention task (measured with BOLD and fMRI) when performed during sleep deprivation versus during rested wakefulness. We find that sleep induced changes in striatal dopamine were associated with changes in cortical brain regions modulated by dopamine (attenuated deactivation of anterior cingulate gyrus and insula) but also in regions that are not recognized targets of dopaminergic modulation (attenuated activation of inferior occipital cortex and cerebellum). Moreover, the increases in striatal dopamine as well as its associated regional activation and deactivation patterns correlated negatively with performance accuracy. These findings therefore suggest that hyperstimulation of D2 receptors in striatum may contribute to the impairment in visual attention during sleep deprivation. Thus, while dopamine increases in prefrontal regions (including stimulation of D1 receptors) may facilitate attention our findings suggest that hyperstimulation of D2 receptors in striatum may impair it. Alternatively, these associations may reflect a compensatory striatal dopamine response (to maintain arousal) that is superimposed on a larger response to sleep deprivation.
Volkow
Nora D
ND
National Institute on Drug Abuse, Bethesda, MD 20892, USA.
Tomasi
Dardo
D
Wang
Gene-Jack
GJ
Telang
Frank
F
Fowler
Joanna S
JS
Wang
Ruiliang L
RL
Logan
Jean
J
Wong
Christopher
C
Jayne
Millard
M
Swanson
James M
JM
D000328:Adult; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D020891:Raclopride / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012892:Sleep Deprivation / Q000000981:diagnostic imaging / Q000378:metabolism*
D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D020891:Raclopride