The nucleus accumbens (NAc) plays an important role in reward, pleasure, laughter, addiction, aggression, fear,and the placebo effect, however, its role in sleep-wake regulation remains unclear.Dopamine D1 and D2 receptor (R) and adeno sine A1 R and A2A R are densely localized in the core and shell of NAc, and have been reported to be critically involved in sleep wake regulation, we hypothesized that NAc might also play an important role in the regulation of sleep-wake cycle.In the pres ent study, we made cell body-specific lesions either in the core or shell of NAc by ibotenic acid, and observed the arousal effects of modafinil and caffeine, which have been reported to be media ted mainly by dopamine receptors and adenosine A-2A R, respec tively.Rats with NAc core lesions exhibited a 26.5% increase in wakefulness, a weaker response in terms of sleep rebound af ter a 6-h sleep deprivation, and less arousal effects of modafinil or caffeine, compared with control rats.Furthermore, these le sioned rats showed a strong response to an ip saline injection, as displayed by a striking 165% prolongation in the latency to sleep.Similarly, the rats with NAc shell lesions showed a 17.4% increase in wakefulness, but the arousal effects of modafinil and caffeine in these lesioned rats were the same as that in con trol rats.These results indicate that both core and shell of the NAc are essential in sleep-wake regulation, with the core being more important than the shell.