Dopaminergic role in stimulant-induced wakefulness

The role of dopamine in sleep regulation and in mediating the effects of wa ke-promoting therapeutics is controversial. In this study, polygraphic reco rdings and caudate microdialysate dopamine measurements in narcoleptic dogs revealed that the wake-promoting antinarcoleptic compounds modafinil and a mphetamine increase extracellular dopamine in a hypocretin receptor 2-indep endent manner. In mice, deletion of the dopamine transporter (DAT) gene red uced non-rapid eye movement sleep time and increased wakefulness consolidat ion independently from locomotor effects. DAT knock-out mice were also unre sponsive to the normally robust wake-promoting action of modafinil, methamp hetamine, and the selective DAT blocker GBR12909 but were hypersensitive to the wake-promoting effects of caffeine. Thus, dopamine transporters play a n important role in sleep regulation and are necessary for the specific wak e-promoting action of amphetamines and modafinil.