Abstract
The role of dopamine in sleep regulation and in mediating the effects of wake-promoting therapeutics is controversial. In this study, polygraphic recordings and caudate microdialysate dopamine measurements in narcoleptic dogs revealed that the wake-promoting antinarcoleptic compounds modafinil and amphetamine increase extracellular dopamine in a hypocretin receptor 2-independent manner. In mice, deletion of the dopamine transporter (DAT) gene reduced non-rapid eye movement sleep time and increased wakefulness consolidation independently from locomotor effects. DAT knock-out mice were also unresponsive to the normally robust wake-promoting action of modafinil, methamphetamine, and the selective DAT blocker GBR12909 but were hypersensitive to the wake-promoting effects of caffeine. Thus, dopamine transporters play an important role in sleep regulation and are necessary for the specific wake-promoting action of amphetamines and modafinil.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1787-1794 |
| Number of pages | 8 |
| Journal | Journal of Neuroscience |
| Volume | 21 |
| Issue number | 5 |
| State | Published - Mar 1 2001 |
| Externally published | Yes |
Keywords
- Amphetamine
- Caffeine
- Dopamine
- Hypocretin
- Modafinil
- Narcolepsy
- Sleep-wake cycle
ASJC Scopus subject areas
- Neuroscience(all)