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

Wake up and smell the dopamine: new mechanisms mediating dopamine activity fluctuations related to sleep and psychostimulant sensitivity.
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DOI:
10.1038/s41386-020-00903-5
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发表时间:
2021-03
期刊:
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子:
--
通讯作者:
Lovinger DM
Lovinger DM
中科院分区:
其他
文献类型:
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作者:
Kesner AJ;Lovinger DM

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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-rapideye-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. In this issue of Neuropsychopharmacology, Alonso and colleagues [7] address these questions by measuring dopamine release at fixed time points after periods of sleep and wake states using brain slice fast-scan cyclic voltammetry (FSCV) in the core subregion of the nucleus accumbens (NAc core). This ventral striatal limbic CNS region was examined as it has prominent roles in control of affect and reward-driven behavior, and previous studies showed circadian fluctuations in dopamine in NAc core [5]. The authors also used immunological techniques to measure cell surface DAT expression and phosphorylation of the DAT protein at threonine 53 (pDAT), a posttranslational modification that enhances DAT function [8].FSCV recordings indicated that the peak level of dopamine release induced by afferent stimulation (DASTIM) occurred shortly after a sleep bout during the light phase, but not the dark phase. Furthermore, the peak DASTIM release was positively correlated with the number of REM bouts across both circadian phases. However,
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在正常和疾病状态下多巴胺转运蛋白调节的机制。
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