Association between striatal dopamine D(2)/D(3) receptors and brain activation during visual attention: effects of sleep deprivation

Sleep deprivation (SD) disrupts dopamine (DA) signaling and impairs attention. However, the interpretation of these concomitant effects requires a better understanding of dopamine’s role in attention processing. Here we test the hypotheses that D(2)/D(3) receptors (D(2)/D(3)R) in dorsal and ventral striatum would distinctly regulate the activation of attention regions and that, by decreasing D(2)/D(3), SD would disrupt these associations. We measured striatal D(2)/D(3)R using positron emission tomography with [(11)C]raclopride and brain activation to a visual attention (VA) task using 4-Tesla functional magnetic resonance imaging. Fourteen healthy men were studied during rested wakefulness and also during SD. Increased D(2)/D(3)R in striatum (caudate, putamen and ventral striatum) were linearly associated with higher thalamic activation. Subjects with higher D(2)/D(3)R in caudate relative to ventral striatum had higher activation in superior parietal cortex and ventral precuneus, and those with higher D(2)/D(3)R in putamen relative to ventral striatum had higher activation in anterior cingulate. SD impaired the association between striatal D(2)/D(3)R and VA-induced thalamic activation, which is essential for alertness. Findings suggest a robust DAergic modulation of cortical activation during the VA task, such that D(2)/D(3)R in dorsal striatum counterbalanced the stimulatory influence of D(2)/D(3)R in ventral striatum, which was not significantly disrupted by SD. In contrast, SD disrupted thalamic activation, which did not show counterbalanced DAergic modulation but a positive association with D(2)/D(3)R in both dorsal and ventral striatum. The counterbalanced dorsal versus ventral striatal DAergic modulation of VA activation mirrors similar findings during sensorimotor processing (Tomasi et al., 2015) suggesting a bidirectional influence in signaling between the dorsal caudate and putamen and the ventral striatum.