Wake up and smell the dopamine: new mechanisms mediating dopamine activity fluctuations related to sleep and psychostimulant sensitivity

Sleep serves a crucial survival function for species across the animal kingdom. Proper sleep not only provides time for rest and metabolic recovery via glial and endocrine functioning, but also contributes critical cognitive processes like memory consolidation and mood stabilization [ 1 ]. Indeed, as highlighted in a recent Neuropsychopharmacology Reviews Series , there is a growing consensus that most, if not all, neuropsychiatric disorders are associated with atypical sleep [ 2 ]. Also at the center of many of these psychiatric illnesses is the neuromodulator dopamine, which, in the central nervous system (CNS), has critical roles in movement control, reward and reinforcement, and affective processes [ 3 ]. Recent studies have also implicated dopaminergic activity in sleep [ 4 ] and have established that dopamine levels and release in the ventral striatum fluctuate in a circadian fashion [ 5 , 6 ]. In rodents, sleep occurs in bouts that are most prominent in the light part of the cycle, but also occur in the dark period [ 1 ], and thus it was not clear from these earlier studies if dopamine fluctuations were related to sleep, time of day, or both. Furthermore, sleep in rodents can be separated into rapid-eye-movement (REM) and non-rapid-eye-movement (NREM) phases that can be distinguished from one another and from the awake state using polysomnography [ 1 ]. The dopamine transporter (DAT), which is responsible for removal/recovery of extracellular dopamine after release also exhibits circadian fluctuations in expression and function [ 5 ]. However, the mechanisms underlying these diurnal changes in dopamine and DAT activity and their relationship to sleep remain unknown.