Parkinson's disease and RLS: the dopaminergic bridge

Dopamine is a neurotransmitter that modulates diverse waking behaviors including movement, motivation, cognition, reward, and feeding. Interest in dopamine's additional contributions to normal and pathologic sleep-wake states has experienced a recent rebirth originating from two clinical disorders: Parkinson's disease and Restless Legs Syndrome. The former, the prototypical disorder of brain dopamine cell loss, is accompanied by marked sleep disruption and impairments in daytime alertness. The latter is exquisitively responsive to pharmacologic agents that act upon dopamine receptors. The potential neurobiological substrates underlying these observations are reviewed here. Converging lines of evidence suggest that mesocorticolimbic dopamine circuits are involved in promoting wakefulness, while a less studied diencephalospinal dopamine system might underly the sensorimotor dysfunction of Restless Legs Syndrome.