The Role of Dopamine and Sleep Research has found that dopamine plays a bigger role in sleep regulation than previously believed. It controls the production of the sleep hormone melatonin. (53) Research suggests that lack of sleep may reduce the number of dopamine receptors. (54)

leep Deprivation Differentially Affects Dopamine Receptor Subtypes in Mouse Striatum Miranda M. Lim,1 Jinbin Xu,2 David M. Holtzman,1 and Robert H. Mach2 Author information ► Copyright and License information ► The publisher's final edited version of this article is available at Neuroreport See other articles in PMC that cite the published article. Go to: Abstract The effects of sleep deprivation on dopaminergic systems remain elusive, in part due to the lack of selective ligands for dopamine receptor subtypes. We examined D1, D2 and D3 receptor density in the mouse brain after sleep deprivation by receptor autoradiography using [3H]SCH 23390 for D1R, [3H]raclopride for D2R, and [3H]WC-10 for D3R (a novel D3R-selective compound developed in our laboratory, not previously reported in mouse). Sleep-deprived mice showed a significant decrease in D1R, no change in D2R, and a significant increase in D3R binding in striatum. This pattern of dopamine receptor changes was not seen in mice subjected to restraint stress, suggesting specificity to sleep. These data provide evidence that brain dopaminergic circuits are remodeled after sleep deprivation. Keywords: Dopamine, Sleep Deprivation, Receptors, Dopamine D1, Receptors, Dopamine D2, Receptors, Dopamine D3, Autoradiography Go to: INTRODUCTION Multiple neurotransmitters are implicated in the sleep-wake cycle. There is recent evidence for the role of dopamine in the regulation of sleep and wakefulness. Microdialysis studies in rat have found that dopamine levels in the prefrontal cortex and nucleus accumbens exhibit a diurnal rhythm [1]. Mice lacking the dopamine transporter gene show increased wakefulness, while mice lacking the dopamine D2 receptor show significantly decreased wakefulness [2,3]. Medications used to maintain wakefulness increase dopaminergic activity by primarily targeting the dopamine transporter reuptake mechanism [4]. In addition, patients with Parkinsons Disease, who show neurodegeneration of the striatonigral dopaminergic system, experience sleep disturbances including excessive daytime sleepiness [5]. Taken together, these studies together suggest a probable role for dopamine in the maintenance of wakefulness. The effects of sleep deprivation on dopamine activity have recently been studied in the human brain using PET radiotracers. Healthy human subjects underwent one night of sleep deprivation and were imaged with [11C]raclopride, which targets primarily D2 receptors with less binding to D3 receptors [6]. [11C]raclopride binding was significantly reduced in the striatum and thalamus. Reduced binding suggests greater endogenous dopamine binding to D2/D3 receptors after sleep deprivation, possibly as a countermeasure to promote wakefulness during sleep deprivation [7]. However, the specific contribution of D3R to sleep deprivation remains to be determined. Until this point it has been difficult to examine D3R due to lack of selective pharmacologic tools. Recently, a novel D3R selective radioligand was developed in our laboratory, [3H]WC-10, or [3H]4-(Dimethylamino)-N-[4-(4-(2-Methoxyphenyl)Piperazin-1-yl)Butyl]Benzamide, a N-phenyl piperazine analog which displays high affinity and selectivity for D3R [8–10]. The first quantitative autoradiographic analysis of the binding of [3H]WC-10 was performed in rat and rhesus monkey brain confirming localization of D3R to the striatum, among other brain regions [9]. The aim of this study is to characterize the effects of sleep deprivation upon D1R, D2R, and D3R binding in mouse striatum. As a comparison to sleep deprivation, we also examined the effects of restraint stress upon D1R, D2R, and D3R binding in mouse striatum. This is the first report of the use of the [3H]WC-10 to localize D3R binding in mouse.