VTA MC3R neurons control feeding in an activity- and sex-dependent manner in mice. (1st October 2021)

• Record Type: Journal Article
• Authors: Dunigan, Anna I.; Olson, David P.; Roseberry, Aaron G.
• Is Part Of: Neuropharmacology. Volume 197(2021)
• Publication Date: 2021-10-01
• Subjects: VTA -- MC3R -- Feeding -- Sex -- DREADD; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2021.108746
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Increasing evidence indicates that the melanocortin and mesolimbic dopamine (DA) systems interact to regulate feeding and body weight. Because melanocortin-3 receptors (MC3R) are highly expressed in the ventral tegmental area (VTA), we tested whether VTA neurons expressing these receptors (VTA MC3R neurons) control feeding and body weight in vivo . We also tested whether there were sex differences in the ability of VTA MC3R neurons to control feeding, as MC3R −/− mice show sex-dependent alterations in reward feeding and DA levels, and there are clear sex differences in multiple DA-dependent behaviors and disorders. Designer receptors exclusively activated by designer drugs (DREADD) were used to acutely activate and inhibit VTA MC3R neurons and changes in food intake and body weight were measured. Acutely altering the activity of VTA MC3R neurons decreased feeding in an activity- and sex-dependent manner, with acute activation decreasing feeding, but only in females, and acute inhibition decreasing feeding, but only in males. These differences did not appear to be due to sex differences in the number of VTA MC3R neurons, the ability of hM3Dq to activate VTA MC3R neurons, or the proportion of VTA MC3R neurons expressing tyrosine hydroxylase (TH). These studies demonstrate an important role for VTA MC3R neurons in the control of feeding and reveal important sex differences in behavior, whereby opposing changes in neuronal activity in male and female mice cause similar changes in behavior. Highlights: MC3Rs are important for feeding, but their exact role is poorly understood. We tested whether altering VTA MC3R neuron activity with DREADDs affected feeding. Acute activation decreased feeding, but only in females. Acute inhibition also decreased feeding, but only in males. Thus, VTA MC3R neurons control feeding in an activity- and sex-dependent manner.