Abstract
Background:
We have previously shown that modafinil promotes wakefulness via dopamine receptor D(1) and D(2) receptors; however, the locus where dopamine acts has not been identified. We proposed that the nucleus accumbens (NAc) that receives the ventral tegmental area dopamine inputs play an important role not only in reward and addiction but also in sleep-wake cycle and in mediating modafinil-induced arousal.
Methodology/principal findings:
In the present study, we further explored the role of NAc in sleep-wake cycle and sleep homeostasis by ablating the NAc core and shell, respectively, and examined arousal response following modafinil administration. We found that discrete NAc core and shell lesions produced 26.5% and 17.4% increase in total wakefulness per day, respectively, with sleep fragmentation and a reduced sleep rebound after a 6-hr sleep deprivation compared to control. Finally, NAc core but not shell lesions eliminated arousal effects of modafinil.
Conclusions/significance:
These results indicate that the NAc regulates sleep-wake behavior and mediates arousal effects of the midbrain dopamine system and stimulant modafinil.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arousal / drug effects
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Arousal / physiology
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Benzhydryl Compounds / pharmacology*
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Central Nervous System Stimulants / pharmacology*
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Electroencephalography
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Male
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Modafinil
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Nucleus Accumbens / drug effects*
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Nucleus Accumbens / pathology*
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Nucleus Accumbens / physiopathology
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Rats
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Rats, Sprague-Dawley
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Sleep / physiology*
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Wakefulness / drug effects*
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Wakefulness / physiology*
Substances
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Benzhydryl Compounds
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Central Nervous System Stimulants
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Modafinil
Grants and funding
This study was supported in part by grants-in-aid for scientific research from the National Natural Science Foundation of China (30970955, 30901797, 31171049, 31171010, 31121061), the Shanghai Committee of Science and Technology (11ZR1401800, 10441901600), National Basic Research Program of China grants (2009CB5220004, 2011CB711004), Shanghai Leading Academic Discipline Project (B119), China National Science and Technology Major Project for Drug Discovery (2009ZX09303-006) and Japan China Medical Association-Chinese Research support funding(2010). The funders had no role in study desigh, data collection and analysis, decision to publish, or preprartion of the manuscript.