Melanin-concentrating hormone (MCH) and MCH-R1 in the locus coeruleus may be involved in the regulation of depressive-like behavior.

Background: Previous anatomical and behavioral studies have shown that melanin-concentrating hormone (MCH) is involved in the modulation of emotional states. However, little is known about brain regions other than the dorsal raphe nucleus that relate the MCH-ergic system to depressive states. Numerous studies have shown that the locus coeruleus (LC) is involved in the regulation of depression and sleep. Although direct physiological evidence is lacking, previous studies suggest that MCH release in the LC decreases neuronal discharge. However, remaining unclear is whether the MCH-ergic system in the LC is related to depressive-like behavior.

Method: We treated rats with an intra-LC injection of MCH, intracerebroventricular injection of MCH, or chronic subcutaneous injections of corticosterone to induce different depressive-like phenotypes. We then assessed the effects of the MCH receptor 1 antagonist SNAP-94847 on depressive-like behavior in the forced swim test (FST) and the sucrose preference test (SPT).

Results: The intra-LC and intracerebroventricular injections of MCH and chronic injections of corticosterone increased immobility time in the FST and decreased sucrose preference in the SPT. All of these depressive-like behaviors were reversed by an intra-LC microinjection of SNAP-94847.

Conclusions: These results suggest that the MCH-ergic system in the LC might play an important role in the regulation of depressive-like behavior.