One-night sleep deprivation decreases striatal and thalamic dopamine D2 receptor availability: Association with impaired cognitive performance and fatigue

Abstract

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Objectives: Across species, the drive to maintain a regular sleep/wake cycle is profound and its disruption hinders daily functioning. The mechanisms through which sleep deprivation (SD) deteriorates performance are poorly understood and dopamine (DA) has been implicated. The objective here is to evaluate effects of SD on brain DA activity and its association with cognitive performance.

Methods: We studied 15 controls with PET using [11C]raclopride (to assess changes in DA) and [11C]cocaine (to assess DA transporters) both during rested wakefulness and after a one night SD. We used distribution volume ratios (Logan et al 1996) to estimate D2 receptor and DA transporter availability. We measured cognitive performance using visual attention (VA) and working memory (WM) tasks.

Results: SD significantly reduced [11C]raclopride binding in caudate (5.5% ±6 p < 0.002), putamen (3.4% ±6. p < 0.05 ) and thalamus (5.3% ±6 p < 0.002), which was interpreted to reflect DA increases with SD. Increases in “sleepiness” correlated with DA increases in caudate (r > 0.72 p < 0.001) and cognitive impairment with DA increases in putamen (r = 0.79, p < 0.001) and thalamus (r = 0.80, p < 0.001). SD did not decrease DA transporters, which indicates that DA changes reflected increases in DA release rather than decreases in DA reuptake.

Conclusions: Inasmuch as DA-enhancing drugs increase wakefulness we postulate that DA increases during SD serve to maintain wakefulness to overcome the drive to sleep. However, the negative correlation with the attention and working memory tasks suggests that this may be at the expense of impaired cognitive performance.