Skip to main content

Activation of Ventral Tegmental Area 5-HT Receptors Reduces Incentive Motivation.

Citation
Valencia-Torres, L., et al. “Activation Of Ventral Tegmental Area 5-Ht Receptors Reduces Incentive Motivation.”. Neuropsychopharmacology : Official Publication Of The American College Of Neuropsychopharmacology, pp. 1511-1521.
Center University of Michigan
Author Lourdes Valencia-Torres, Cristian M Olarte-Sánchez, David J Lyons, Teodora Georgescu, Megan Greenwald-Yarnell, Martin G Myers, Christopher M Bradshaw, Lora K Heisler
Abstract

Obesity is primarily due to food intake in excess of the body's energetic requirements, intake that is not only associated with hunger but also the incentive value of food. The 5-hydroxytryptamine 2C receptor (5-HTR) is a target for the treatment of human obesity. Mechanistically, 5-HTRs are positioned to influence both homeostatic feeding circuits within the hypothalamus and reward circuits within the ventral tegmental area (VTA). Here we investigated the role of 5-HTRs in incentive motivation using a mathematical model of progressive ratio (PR) responding in mice. We found that the 5-HTR agonist lorcaserin significantly reduced both ad libitum chow intake and PR responding for chocolate pellets and increased c-fos expression in VTA 5-HTR expressing γ-aminobutyric acid (GABA) neurons, but not 5-HTR expressing dopamine (DA) neurons. We next adopted a chemogenetic approach using a 5-HTR line to clarify the function of subset of 5-HT receptor expressing VTA neurons in the modulation of appetite and food-motivated behavior. Activation of VTA 5-HT receptor expressing neurons significantly reduced ad libitum chow intake, operant responding for chocolate pellets, and the incentive value of food. In contrast, chemogenetic inhibition of VTA 5-HT receptor expressing neurons had no effect on the feeding behavior. These results indicate that activation of the subpopulation of 5-HTR neurons within the VTA is sufficient to significantly reduce homeostatic feeding and effort-based intake of palatable food, and that this subset has an inhibitory role in motivational processes. These findings are relevant to the treatment of obesity.

Year of Publication
2017
Journal
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Volume
42
Issue
7
Number of Pages
1511-1521
Date Published
06/2017
ISSN Number
1740-634X
DOI
10.1038/npp.2016.264
Alternate Journal
Neuropsychopharmacology
PMID
27882999
PMCID
PMC5362069
Download citation