Nucleus accumbens melanin-concentrating hormone signaling promotes feeding in a sex-specific manner

• Published in: Neuropharmacology 2020-11, Vol.178, p.108270-108270, Article 108270
• Main Authors: Terrill, Sarah J., Subramanian, Keshav S., Lan, Rae, Liu, Clarissa M., Cortella, Alyssa M., Noble, Emily E., Kanoski, Scott E.
• Format: Article
• Language: English
• Subjects: Animals; Estrogen; Feeding Behavior - physiology; Feeding Behavior - psychology; Female; Food intake; Food reward; Hypothalamic Hormones - analysis; Hypothalamic Hormones - metabolism; Male; MCH; Melanins - analysis; Melanins - metabolism; Neural Pathways - chemistry; Neural Pathways - metabolism; Nucleus accumbens; Nucleus Accumbens - chemistry; Nucleus Accumbens - metabolism; Pituitary Hormones - analysis; Pituitary Hormones - metabolism; Rats; Rats, Sprague-Dawley; Sex Characteristics; Sex differences; Signal Transduction - physiology
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2020.108270

Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide produced in the lateral hypothalamus and zona incerta that increases food intake. The neuronal pathways and behavioral mechanisms mediating the orexigenic effects of MCH are poorly understood, as is the extent to which MCH-mediated feeding outcomes are sex-dependent. Here we investigate the hypothesis that MCH-producing neurons act in the nucleus accumbens shell (ACBsh) to promote feeding behavior and motivation for palatable food in a sex-dependent manner. We utilized ACBsh MCH receptor (MCH1R)-directed pharmacology as well as a dual virus chemogenetic approach to selectively activate MCH neurons that project to the ACBsh. Results reveal that both ACBsh MCH1R activation and activating ACBsh-projecting MCH neurons increase consumption of standard chow and palatable sucrose in male rats without affecting motivated operant responding for sucrose, general activity levels, or anxiety-like behavior. In contrast, food intake was not affected in female rats by either ACBsh MCH1R activation or ACBsh-projecting MCH neuron activation. To determine a mechanism for this sexual dimorphism, we investigated whether the orexigenic effect of ACBsh MCH1R activation is reduced by endogenous estradiol signaling. In ovariectomized female rats on a cyclic regimen of either estradiol (EB) or oil vehicle, ACBsh MCH1R activation increased feeding only in oil-treated rats, suggesting that EB attenuates the ability of ACBsh MCH signaling to promote food intake. Collective results show that MCH ACBsh signaling promotes feeding in an estrogen- and sex-dependent manner, thus identifying novel neurobiological mechanisms through which MCH and female sex hormones interact to influence food intake. •ACBsh-projecting MCH neuron activation promotes eating in males but not females.•Endogenous estrogen signaling counteracts ACBsh MCH-mediated orexigenic effects.•ACBsh MCH signaling does not influence locomotor activity or anxiety-like behavior.