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Dopamine is the most abundant of monoamines in the central nervous system (CNS). It modulates diverse behaviors including movement, motivation/reward, cognition, and feeding that share one notable attribute in common: they all play out on a backdrop of wakefulness (Bjorklund and Lindvall 1984; Marin et al. 1998; Durstewitz et al. 1999; Williams and Goldman-Rakic 1998). Dopamine's influence(s) upon normal and pathologic wake–sleep has unfortunately only recently begun to receive more widespread attention. The rebirth of interest in dopamine's participation in wake–sleep behaviors comes straight from the clinical arena. Here, sleepiness has been noted to be a common and disabling feature attending midbrain dopamine cell loss in Parkinson's disease (PD), as well as with dopamine agonist treatment of PD and additional disorders that interfere with normal sleep such as restless legs syndrome, and periodic leg movement and rapid eye movement sleep disorders (Rye 2004a,b; Rye and Jankovic 2002). Although this clinical experience argues that dopamine signaling is integral to maintaining wakefulness, a complete understanding is only beginning to emerge from recent scientific inquiries. What follows is a comprehensive account of the current state of knowledge of the brain's dopamine pathways as it pertains to their modulation of normal and pathologic wake–sleep state(s).
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