The dopaminergic dilema: Sleep or wake? Implications in Parkinson's disease

The neurobiology of sleep has been quickly developed in the recent years, but the same progress of knowledge obtained for several neurotransmitters and neuropeptides were not accomplished for dopamine (DA). In fact, controversial opinions about the function of DA on sleep–wake regulation argue. The debate resides on the demonstration that DA is a substance dramatically related to sleep processes, and not associated exclusively with wakefulness events. In this sense, recent data from literature reveal that REM sleep neural pathways are triggered when D2 dopaminergic receptors are activated on a background of reduced mesolimbic glutamatergic and serotonergic tone. Furthermore, selective lesion of the substantia nigra pars compacta (SNpc) neurons elicits a remarkable disruption of REM sleep. Additionally, the overall mean firing rate of the ventral tegmental area (VTA) neurons, present a large increase in the burst firing during REM sleep episodes. Such evidence prompts us to speculate that dopaminergic neurons present at SNpc and VTA could be consider essential for sleep regulation, in particular for triggering and maintenance of REM sleep, respectively. A clinical corroboration of this hypothesis concerned a study of motor restoration control, observed during REM sleep in Parkinson's disease (PD) patients. We propose that the paradigm of DA is being involved with wakefulness and not sleep regulation is not fully accurate. The premise stated in the current manuscript allegates that DA could present an important participation in both sleep and wake states, and each state may be accounted by differential degrees of dopaminergic modulation. The conclusion drawn from these findings is that DA has significant implications in the sleep regulation, and that particular condition has to be fully considered in respect of treatment and management of PD patients.