Emerging views of dopamine in modulating sleep/wake state from an unlikely source: PD

Monoamines (e.g., serotonin [5-HT], norepinephrine [NE], histamine [HA]), and acetylcholine (ACh) modulate wakefulness and slow-wave and REM sleep. Inhibition of wake-promoting ACh and HA neurons by extracellular accumulation of adenosine, and the forebrain ventrolateral preoptic area, are critical for initiating sleep. The recently discovered neuropeptide hypocretin is important in maintaining wakefulness because it excites each of the above neurotransmitter-containing cell groups and when deficient, results in narcolepsy/cataplexy.1 Dopamine (DA) traditionally has not been considered a modulator of sleep/wake state in part because of claims that endogenous DA transmission varies little between sleep/wake states. Thus, recent clinical recognition of daytime sleepiness in PD has been met with surprise and has prompted a search for its cause(s).2,3⇓ A decades-long debate as to whether DA participates in behavioral state control—and if it does, what its role(s) might be—has been rekindled. This issue of Neurology includes one study documenting daytime sleepiness with the D2–D3 receptor agonist ropinirole in drug-naïve control subjects4 and three investigating the pathophysiologic basis of like decrements seen in the face of DA deficiency accompanying PD.5-7⇓⇓ In an upcoming issue, a fifth work reports on physiologically defined sleepiness in patients with PD who reported sleepiness, as well as its clinicoetiologic correlates.8 That sleepiness is common not only with D2–D3 agonist use but also with endogenous DA loss is seemingly paradoxical, and this highlights the complexity of the influences of DA on the sleep/wake state.