Activation of ventral tegmental area dopamine neurons produces wakefulness through dopamine D₂-like receptors in mice

A growing body of evidence suggests that dopamine plays a role in sleep–wake regulation, but the dopamine-producing brain areas that control sleep–wake states are unclear. In this study, we chemogenetically activated dopamine neurons in the ventral midbrain of mice to examine the role of these neurons in sleep–wake regulation. We found that activation of dopamine neurons in the ventral tegmental area (VTA), but not in the substantia nigra, strongly induced wakefulness, although both cell populations expressed the neuronal activity marker c-Fos after chemogenetic stimulation. Analysis of the pattern of behavioral states revealed that VTA activation increased the duration of wakefulness and decreased the number of wakefulness episodes, indicating that wakefulness was consolidated by VTA activation. The increased wakefulness evoked by VTA activation was completely abolished by pretreatment with the dopamine D₂/D₃ receptor antagonist raclopride, but not by the D₁ receptor antagonist SCH23390. These findings indicate that the activation of VTA dopamine neurons promotes wakefulness via D₂/D₃ receptors.