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Publication : VTA MC3R neurons control feeding in an activity- and sex-dependent manner in mice.

First Author  Dunigan AI Year  2021
Journal  Neuropharmacology Volume  197
Pages  108746 PubMed ID  34371079
Mgi Jnum  J:350400 Mgi Id  MGI:6789770
Doi  10.1016/j.neuropharm.2021.108746 Citation  Dunigan AI, et al. (2021) VTA MC3R neurons control feeding in an activity- and sex-dependent manner in mice. Neuropharmacology 197:108746
abstractText  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.
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