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

Abstract

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 oiltreated rats, suggesting that EB attenuates the ability of ACBsh MCH signaling to promote food intake. Collective results show that that MCH ACBsh signaling promotes feeding in an estrogenand sex-dependent manner, thus identifying novel neurobiological mechanisms through which MCH and female sex hormones interact to influence food intake..

Distinct neuropeptide-receptor modules regulate a sex-specific behavioral response to a pheromone

“…Multiple hormonal receptors are involved in regulating the induction of A. aegyptii ecdysteroid hormone production through two different neuropeptide signaling systems: ILP3 initiates digestion of the blood meal 69 , while OEH stimulates oocyte yolk uptake 70 . Melanin-concentrating hormone is a neuropeptidergic hormone that promotes appetite and feeding behaviors in mice in a sex-dependent manner 71 . Meanwhile, age-dependent changes in levels of Neuropeptide F result in the promotion of survival-benefiting appetitive memory in Drosophila , concurrent with the impairment of memories associated with insufficient survival benefits 72 .…”

Food cue reactivity: Neurobiological and behavioral underpinnings

“…Given that palatable food-associated olfactory cues stimulate ghrelin release [ 48 ], that HPCv GHSR1a-to-LHA signaling functionally targets LHA orexin neurons to enhance eating [ 52 ], and that both mPFC orexin receptor signaling and LHA-mPFC signaling are necessary for CPF [ 39 ], a putative model emerges in which exposure to cues associated with palatable food stimulates peripheral ghrelin release, which crosses the blood–brain-barrier to engage a [HPCv GHSR1a]-to-[LHA orexin neurons]-to-[mPFC] pathway to promote CPF. More research is required to understand the neural pathways through which MCH mediates CPF [ 53 , 54 ].…”

Distinct Neuropeptide-Receptor Modules Regulate a Sex-Specific Behavioral Response to a Pheromone

“…Multiple hormonal receptors are involved in regulating the induction of A. aegyptii ecdysteroid hormone production through two different neuropeptide signaling systems: ILP3 initiates digestion of the blood meal 57 , while OEH stimulates oocyte yolk uptake 58 . Melanin-concentrating hormone is a neuropeptidergic hormone that promotes appetite and feeding behaviors in mice in a sex-dependent manner 59 . Meanwhile, age-dependent changes in levels of Neuropeptide F result in the promotion of survival-benefiting appetitive memory in Drosophila, concurrent with the impairment of memories associated with insufficient survival benefits 60 .…”