The Effects of Melanin-Concentrating Hormone on Neurotransmitter Systems Involved in the Generation and Maintenance of Wakefulness

Within the central nervous system (CNS), melanin-concentrating hormone (MCH) participates in a number of functions including sleep-wake behavior. In this respect, MCHergic neurons project widely throughout the central nervous system (CNS) to neural structures involved in the regulation of wakefulness (W). An enhancement of REM sleep time has been described following the microinjection of MCH into the dorsal raphe nucleus (serotonergic neurons), locus coeruleus nucleus (noradrenergic neurons), and basal forebrain [(horizontal limb of the diagonal band of Broca) glutamatergic and cholinergic (W-on) neurons] of rodents. In addition, optogenetic stimulation of MCH terminals in the tuberomammillary nucleus (histaminergic neurons) is followed by an increase in the duration of REM sleep episodes. Moreover, the finding that the neuropeptide negatively modulates the mesolimbic dopaminergic function tends to indicate that the inhibition of nucleus accumbens and ventral tegmental nucleus dopaminergic neurons by MCH could facilitate the occurrence of REM sleep. Thus, the REM sleep-inducing and sleep-facilitating effect of MCH is at least partly related to the deactivation of monoaminergic, glutamatergic, and cholinergic (W-on) neurons.