In the model used in the present study, we did not find histaminergic H1 receptors to be involved in the desynchronization effects of modafinil, suggesting that modafinil exerts EEG desynchronization mediated by different receptor mechanisms according to different models. The administration of either low or high doses of D2R agonist to rats that have already been treated with D1R antagonist elicits a marked 
sedative response associated with EEG synchronization, and the effects can be prevented by D2R blockers. This suggests that D1R plays an important role in the mediation of EEG desynchronization. D2R KO mice have been shown to exhibit a significant decrease in the power density of nonrapid-eye-movement sleep over the frequency range of the delta activity during the dark period. However, pretreatment with D2R antagonist at doses that preferentially acts at presynaptic sites reversed the effects of low doses of D2R agonist. This suggested that the EEG synchronization induced by D2R agonist was mainly mediated by presynaptic D2R. Although modafinil is known to affect multiple neurotransmitter systems, such as catecholamines, serotonin, glutamate, GABA, orexin, and histamine, this drug increases extracellular levels of DA in the nucleus accumbens and medial prefrontal cortex. By using D2R knockout mice in combination with a DA D1R antagonist, we reported that both D1R and D2R are essential to the arousal effects of modafinil, with especially D2R being more important than D1R in these effects. The results suggested that modafinil enhances extracellular levels of DA mainly by targeting at D2R. D2R and adenosine A2AR are colocalized in the NAc. Together with other recent data, we proposed that adenosine acting on excitatory A2ARs can modulate the activity of GABAergic output neurons in the NAc to inhibit arousal and promote sleep. On the other hands, activation of the inhibitory D2R system suppresses the GABAergic neurons in the NAc to disinhibit the inhibitory actions to arousal systems and promote wakefulness. In the present study, desynchonization AbMole Miglitol models by scopolamine and reserpine are different from synchronized pattern of non-rapid-eye-movement sleep. We found that D1R might be more important than D2R in the mediation of modafinil-induced EEG desynchronization. In addition, a1-adrenoceptors are also involved in the response. Adrenergic signaling in the CNS plays a prominent role in the AbMole Trihexyphenidyl HCl timing of sleep states and in the regulation of changes in EEG. a1-adrenoceptor agonist and a2-adrenoceptor antagonists, which increase noradrenergic transmission, induce a decrease in delta power and promote wakefulness. A wealth of pharmacological data demonstrates the necessity of adrenergic receptors in the response to modafinil.