The involvement of dopamine in the modulation of sleep and waking

Dopamine (DA)-containing neurons involved in the regulation of sleep and waking (W) arise in the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNc). The VTA and SNc cells have efferent and afferent connections with the dorsal raphe nucleus (DRN), the pedunculopontine and laterodorsal tegmental nuclei (PPT/LDT), the locus coeruleus (LC), the lateral and posterior hypothalamus (LH), the basal forebrain (BFB), and the thalamus. Molecular cloning techniques have enabled the characterization of two distinct groups of DA receptors, D(1)-like and D(2)-like receptors. The D(1) subfamily includes the D(1) and D(5) receptors, whereas the D(2) subfamily comprises the D(2), D(3), and D(4) receptors. Systemic administration of a selective D(1) receptor agonist induces behavioral arousal, together with an increase of W and a reduction of slow wave sleep (SWS) and REM sleep (REMS). Systemic injection of a DA D(2) receptor agonist induces biphasic effects, such that low doses reduce W and increase SWS and REMS (predominant activation of the D(2) autoreceptor), whereas large doses induce the opposite effect (predominant facilitation of the D(2) postsynaptic receptor). Compounds with DA D(1) or D(2) receptor blocking properties augment non-REMS and reduce W. Preliminary findings tend to indicate that the administration of a DA D(3)-preferring agonist induces somnolence and sleep in laboratory animals and man. DA neurons in the VTA and the SNc do not change their mean firing rate across the sleep-wake cycle. It has been proposed that DA cells in the midbrain show a change in temporal pattern rather than firing rate during the sleep-wake cycle. The available evidence tends to indicate that during W there occurs an increase of burst firing activity of DA neurons, and an enhanced release of DA in the VTA, the nucleus accumbens (NAc), and a number of forebrain structures. A series of structures relevant for the regulation of the behavioral state, including the DRN, LDT/PPT, LC, and LH, could be partly responsible for the changes in the temporal pattern of activity of DA neurons.