Abstract
The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons of the lateral sector of the posterior hypothalamus and zona incerta. MCHergic neurons project throughout the central nervous system, including areas such as the dorsal (DR) and median (MR) raphe nuclei, which are involved in the control of sleep and mood. Major Depression (MD) is a prevalent psychiatric disease diagnosed on the basis of symptomatic criteria such as sadness or melancholia, guilt, irritability, and anhedonia. A short REM sleep latency (i.e., the interval between sleep onset and the first REM sleep period), as well as an increase in the duration of REM sleep and the density of rapid-eye movements during this state, are considered important biological markers of depression. The fact that the greatest firing rate of MCHergic neurons occurs during REM sleep and that optogenetic stimulation of these neurons induces sleep, tends to indicate that MCH plays a critical role in the generation and maintenance of sleep, especially REM sleep. In addition, the acute microinjection of MCH into the DR promotes REM sleep, while immunoneutralization of this peptide within the DR decreases the time spent in this state. Moreover, microinjections of MCH into either the DR or MR promote a depressive-like behavior. In the DR, this effect is prevented by the systemic administration of antidepressant drugs (either fluoxetine or nortriptyline) and blocked by the intra-DR microinjection of a specific MCH receptor antagonist. Using electrophysiological and microdialysis techniques we demonstrated also that MCH decreases the activity of serotonergic DR neurons. Therefore, there are substantive experimental data suggesting that the MCHergic system plays a role in the control of REM sleep and, in addition, in the pathophysiology of depression. Consequently, in the present report, we summarize and evaluate the current data and hypotheses related to the role of MCH in REM sleep and MD.
Highlights
The search for new pharmacological strategies to treat psychiatric disorders is a “hot topic” in neuroscience
Utilizing the in vivo microdialysis technique, it has been shown that the release of melanin-concentrating hormone (MCH) in the amygdala of patients with treatment-resistant epilepsy is minimal during active wakefulness with social interactions, increases after eating, and reaches a maximum level at sleep onset (Blouin et al, 2013)
Preliminary studies in cats have shown that MCH microinjections into the DR produced an increase in REM or NREM sleep depending on the exact location of the microinjection sites (Devera et al, 2007)
Summary
The search for new pharmacological strategies to treat psychiatric disorders is a “hot topic” in neuroscience. These neurons have a very low frequency of discharge during wakefulness, their firing rate increases slightly during NREM sleep and reaches the maximum level of activation during REM sleep (Hassani et al, 2009).
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