Functional Interactions Between MCHergic and Dopaminergic Neurons: Role in the Control of Wakefulness and Sleep

Abstract

Dopamine (DA) plays an important role in emotional arousal. In addition, recent studies have demonstrated that there is an increase in DAergic activity both in the nucleus accumbens and prefrontal cortex during rapid-eye-movement (REM) sleep; this DAergic activity has been involved in the generation of dreams. The melanin-concentrating hormone (MCH) is a peptide with neuromodulatory functions synthesized by neurons located in the postero-lateral hypothalamus and incerto-hypothalamic area. MCHergic neurons project throughout the central nervous system, including the substantia nigra pars compacta and ventral tegmental area, where DAergic neurons are located. MCH controls energy homeostasis, with a main role in energy conservation. In agreement with the energy-conserving function of sleep, MCH promotes sleep. In comparison to wakefulness (W), MCHergic neurons increase their firing rate during non-REM (NREM) sleep and reach their maximal rate during REM sleep. Although there is almost no direct information regarding the interaction between MCHergic and DAergic neurons in the control of W and sleep, indirect evidence strongly suggests an important interaction between both systems in the control of these behavioral states. MCHergic fibers and receptors are present in the DAergic mesocorticolimbic system, a key center for activation and motivation. Furthermore, the absence of MCH leads to an increase in DA release and the up-regulation of DA receptors that is known to facilitate the generation of W. On the other hand, DA decreases the release of MCH; this fact would also promote W. While both systems seem to have opposite effects in the generation of W, they appear to have complementary roles in the regulation of different aspects of REM sleep. In conclusion, although more experimental data is needed, available evidence tends to indicate that functional interactions between the MCHergic and DAergic systems play an important role in the control of behavioral states.