The Role Of Nucleus Accumbens In The Regulation Of Sleep Awakening

Nucleus accumbens (NAc) is the nucleus ventral to the caudate nucleus and dorsal to the olfactory tubercle in rats, in the basal forbrain and forms the main part of the ventral striatun. Further more, NAc can be divided into the outer medial, ventral and lateral shell and the more dorally and centrally located core subregion. In these two area, studies showed that various neurochemical substances, neurotransmitters and receptors show differential distribution patterns. As the interface between the limbic system and the motor regulated structures, NAc plays its roles in a lot of physiological function, such as drug addiction, rewarding system, locomotor activity, exploratory behavior and food taking. However, there is few people focus on its role in the sleep-regulating. Following the results of Mei-Hong Qiu in our own lab, a lesion to the core of NAc could increase the wakefulness in rats. Based on this finding, we separately introduced the lesion to the core and the shell of the NAc to elucidate the role of this nucleus in the sleep-wake regulation.NAc is one of the area which have the most A2A receptors in the brain. We discovered that A2A receptor mediated the arousal effect of caffeine, which has been published in2005. NAc has aboundant D1and D2receptor, which receives most projection from Ventral tegmental area(VTA),where mesolimbic dopaminergic systems originate. It has been well-illustrated that dopamine has its effects on the sleep-wake behavior, that people suffered Parkinson’s disease, with the lost of the dopamine neurons, always have sleep disorder. Modafinil, as a wakefulness-inducing medicine, could enhance the dopamine release in the NAc. We also found that dopaminergic D1and D2receptors were essential for the wakefulness induced by modafinil. Therefore, we use chemical lesion, nucleus injection and local gene knockdown to explore the function of the adenosine A2A receptor, dopamine D1and D2receptors in the NAc in the regulation of the sleep-waking behavior.RESULTS1, Both the lesion of core and shell induced increased wakefulness and the fragmentation of NREM sleep in the daytime, and the core lesion had larger effect. Only the lesion of core destroyed the homeostasis of sleep, but not the lesion of shell.2, The lesion of core also eliminated the arousal effect of modafinil, but had no effect on caffeine-induced wakefulness, while the lesion of shell had no effect on the arousal effect of these two drugs.3, Modafinil-induced wakefulness was eliminated by pre-injection of raclopride, a kind of dopamine D2receptor antagonist, into the NAc core. Local pre-injection of saline and SCH23390, a kind of dopamine D1receptor antagonist, into the NAc core had no effect on the arousal effect of modafinil.4, Injection the siRNA into the NAc core to knockdown the local D2receptor expression, prolonged NREM sleep and reduced wakefulness at night. CONCLUSION Our results suggest that NAc core and shell take part in sleep-wake regulation in rats. The NAc core plays a potent role in the homeostasis regulation of sleep. Dopamine D2receptors in the NAc core is the target of modafinil, and they play an essential role in the physiological maintenance of wakefulness.