Dopamine and Wakefulness: Pharmacology, Genetics, and Circuitry.

Over the period of decades in the mid to late twentieth century, arousal-promoting functions were attributed to neuromodulators including serotonin, hypocretin, histamine, and noradrenaline. For some time, a relatively minor role in regulating sleep and wake states was ascribed to dopamine and the dopamine-producing cells of the ventral tegmental area, despite the fact that dopaminergic signaling is a major target, if not the primary target, for wake-promoting agents. In recent years, due to observations from human genetic studies, pharmacogenetic studies in animal models, and the increasingly sophisticated methods used to manipulate the nervous systems of experimental animals, it has become clear that dopaminergic signaling is central to the regulation of arousal. This chapter reviews this central role of dopaminergic signaling, and in particular its antagonistic interaction with adenosinergic signaling, in maintaining vigilance and in the response to wake-promoting therapeutics.