» Articles » PMID: 34371079

VTA MC3R Neurons Control Feeding in an Activity- and Sex-dependent Manner in Mice

Overview
Specialties Neurology
Pharmacology
Date 2021 Aug 9
PMID 34371079
Citations 6
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Overlapping representations of food and social stimuli in VTA dopamine neurons.

Willmore L, Minerva A, Engelhard B, Murugan M, McMannon B, Oak N bioRxiv. 2023; .

PMID: 37293057 PMC: 10245666. DOI: 10.1101/2023.05.17.541104.


Neuropeptides Modulate Feeding via the Dopamine Reward Pathway.

Jin R, Sun S, Hu Y, Zhang H, Sun X Neurochem Res. 2023; 48(9):2622-2643.

PMID: 37233918 DOI: 10.1007/s11064-023-03954-4.


Actions of feeding-related peptides on the mesolimbic dopamine system in regulation of natural and drug rewards.

Dunigan A, Roseberry A Addict Neurosci. 2023; 2.

PMID: 37220637 PMC: 10201992. DOI: 10.1016/j.addicn.2022.100011.


Melanocortin receptor 3 and 4 mRNA expression in the adult female Syrian hamster brain.

Hall M, Kohut-Jackson A, Peyla A, Friedman G, Simco N, Borland J Front Mol Neurosci. 2023; 16:1038341.

PMID: 36910260 PMC: 9995703. DOI: 10.3389/fnmol.2023.1038341.


Organization of neural systems expressing melanocortin-3 receptors in the mouse brain: Evidence for sexual dimorphism.

Bedenbaugh M, Brener S, Maldonado J, Lippert R, Sweeney P, Cone R J Comp Neurol. 2022; 530(16):2835-2851.

PMID: 35770983 PMC: 9724692. DOI: 10.1002/cne.25379.


References
1.
Xu A, Ste-Marie L, Kaelin C, Barsh G . Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding. Endocrinology. 2006; 148(1):72-80. DOI: 10.1210/en.2006-1119. View

2.
Wang S, Tan Y, Zhang J, Luo M . Pharmacogenetic activation of midbrain dopaminergic neurons induces hyperactivity. Neurosci Bull. 2013; 29(5):517-24. PMC: 5561950. DOI: 10.1007/s12264-013-1327-x. View

3.
Kim J, Ganesan S, Luo S, Wu Y, Park E, Huang E . Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain dopaminergic neurons. Science. 2015; 350(6256):102-6. PMC: 4725325. DOI: 10.1126/science.aac4690. View

4.
Stamatakis A, Jennings J, Ung R, Blair G, Weinberg R, Neve R . A unique population of ventral tegmental area neurons inhibits the lateral habenula to promote reward. Neuron. 2013; 80(4):1039-53. PMC: 3873746. DOI: 10.1016/j.neuron.2013.08.023. View

5.
van Zessen R, Phillips J, Budygin E, Stuber G . Activation of VTA GABA neurons disrupts reward consumption. Neuron. 2012; 73(6):1184-94. PMC: 3314244. DOI: 10.1016/j.neuron.2012.02.016. View