The role of nucleus accumbens core/shell in sleep-wake regulation and their involvement in modafinil-induced arousal

• Published in: PloS one 2012-09, Vol.7 (9), p.e45471-e45471
• Main Authors: Qiu, Mei-Hong, Liu, Wei, Qu, Wei-Min, Urade, Yoshihiro, Lu, Jun, Huang, Zhi-Li
• Format: Article
• Language: English
• Subjects: Addictions; Adenosine; Animals; Arousal; Arousal - drug effects; Arousal - physiology; Benzhydryl Compounds - pharmacology; Biology; Caffeine; Central Nervous System Stimulants - pharmacology; Dopamine; Dopamine D1 receptors; Dopamine D2 receptors; Dosage and administration; Electroencephalography; Homeostasis; Laboratory animals; Laws, regulations and rules; Lesions; Light; Male; Medicine; Mesencephalon; Modafinil; Nervous system agents; Neurobiology; Neurosciences; Nuclei; Nucleus accumbens; Nucleus Accumbens - drug effects; Nucleus Accumbens - pathology; Nucleus Accumbens - physiopathology; Pharmacology; Physiological aspects; Prevention; Rats; Rats, Sprague-Dawley; Receptors; Reinforcement; Rodents; Sleep; Sleep - physiology; Sleep and wakefulness; Sleep deprivation; Sleep disorders; Ventral tegmentum; Wakefulness; Wakefulness - drug effects; Wakefulness - physiology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0045471

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. 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. These results indicate that the NAc regulates sleep-wake behavior and mediates arousal effects of the midbrain dopamine system and stimulant modafinil.