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Publication : Essential role of dopamine D2 receptor in the maintenance of wakefulness, but not in homeostatic regulation of sleep, in mice.

First Author  Qu WM Year  2010
Journal  J Neurosci Volume  30
Issue  12 Pages  4382-9
PubMed ID  20335474 Mgi Jnum  J:159216
Mgi Id  MGI:4442094 Doi  10.1523/JNEUROSCI.4936-09.2010
Citation  Qu WM, et al. (2010) Essential role of dopamine D2 receptor in the maintenance of wakefulness, but not in homeostatic regulation of sleep, in mice. J Neurosci 30(12):4382-9
abstractText  Dopamine (DA) and its D(2) receptor (R) are involved in cognition, reward processing, and drug addiction. However, their roles in sleep-wake regulation remain unclear. Herein we investigated the role of D(2)R in sleep-wake regulation by using D(2)R knock-out (KO) mice and pharmacological manipulation. Compared with WT mice, D(2)R KO mice exhibited a significant decrease in wakefulness, with a concomitant increase in non-rapid eye movement (non-REM, NREM) and REM sleep and a drastic decrease in the low-frequency (0.75-2 Hz) electroencephalogram delta power of NREM sleep, especially during the first 4 h after lights off. The KO mice had decreased mean episode duration and increased episode numbers of wake and NREM sleep, many stage transitions between wakefulness and NREM sleep during the dark period, suggesting the instability of the wake stage in these D(2)R KO mice. When the KO mice were subjected to a cage change or an intraperitoneal saline injection, the latency to sleep in the KO mice decreased to half of the level for WT mice. The D(2)R antagonist raclopride mimicked these effects in WT mice. When GBR12909, a dopamine transport inhibitor, was administered intraperitoneally, it induced wakefulness in WT mice in a dose-dependent manner, but its arousal effect was attenuated to one-third in the D(2)R KO mice. However, these 2 genotypes showed an identical response in terms of sleep rebound after 2, 4, and 6 h of sleep deprivation. These results indicate that D(2)R plays an essential role in the maintenance of wakefulness, but not in homeostatic regulation of NREM sleep.
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