Research ReportImmunoneutralization of melanin-concentrating hormone (MCH) in the dorsal raphe nucleus: Effects on sleep and wakefulness

Hypothalamic neurons that utilize melanin-concentrating hormone (MCH) as a neuromodulator exert a positive control over energy homeostasis, inducing feeding and decreasing metabolism. Recent studies have shown also that this system plays a role in the generation and/or maintenance of sleep. MCHergic neurons project to the serotonergic dorsal raphe nucleus (DR), a neuroanatomical structure involved in several functions during wakefulness (W), and in the regulation of rapid-eye movements (REM) sleep. Recently, we determined the effect of MCH microinjected into the DR on sleep variables in the rat. MCH produced a marked increment of REM sleep, whereas slow wave sleep (SWS) showed only a moderate increase. In the present study, we analyze the effect of immunoneutralization of MCH in the DR on sleep and W in the rat. Compared to the control solution, microinjections of anti-MCH antibodies (1/100 solution in 0.2 μl) induced a significant increase in REM sleep latency (31.2 ± 7.1 vs. 84.2 ± 24.8 min, p < 0.05) and a decrease of REM sleep time (37.8 ± 5.4 vs. 17.8 ± 2.9 min, p < 0.05) that was related to the reduction in the number of REM sleep episodes. In addition, there was an increase of total W time (49.8 ± 4.6 vs. 72.0 ± 5.7 min, p < 0.01). Light sleep and SWS remained unchanged. The intra-DR administration of a more diluted solution of anti-MCH antibodies (1/500) or rabbit pre-immune serum did not modify neither W nor REM sleep variables. Our findings strongly suggest that MCH released in the DR facilitates the occurrence of REM sleep.

Research Highlights► MCHergic system plays a role in the generation and/or maintenance of sleep. ► In previous report we determined that MCH applied in the DR increased REM sleep. ► We studied the effects of anti-MCH antibodies in the DR on sleep variables. ► Immunoneutralization of MCH in DR decreased REM sleep time and increased wakefulness. ► We concluded that endogenous MCH released in DR facilitates REM sleep.