Melanin-concentrating hormone (MCH) modulates the activity of dorsal raphe neurons

Hypothalamic neurons that utilize melanin-concentrating hormone (MCH) as a neuromodulator are localized in the postero-lateral hypothalamus and incerto-hypothalamic area. These neurons send dense projections to the dorsal raphe nucleus (DRN). Serotonergic neurons of the DRN are involved in the control of sleep and play a critical role in major depression. Previously, we demonstrated that microinjections of MCH into the DRN resulted in an increase in REM sleep and produce a depressive-like effect. In the present study we examined the mechanisms that mediate these effects by employing neuroanatomical and electrophysiological techniques. First, we determined that rhodamine-labeled MCH (R-MCH), when microinjected into the lateral ventricle, is internalized in serotonergic and non-serotonergic DRN neurons in rats and cats. These data strongly suggest that these neurons express MCHergic receptors. Second, in rats, we demonstrated that the microinjection of MCH into the lateral ventricle results in a significant decrease in the firing rate in 59% of the neurons recorded in the DRN; the juxtacellular administration of MCH reduced the discharge in 80% of these neurons. Some of the neurons affected by MCH were likely serotonergic on the basis of their electrophysiological and pharmacological properties. We conclude that MCH reduces the activity of serotonergic neurons of the DRN. These and previous data suggest that the MCHergic modulation of serotonergic activity within the DRN is involved in the regulation of REM sleep as well as in the pathophysiology of depressive disorders.