The food intake-suppressive effects of glucagon-like peptide-1 receptor signaling in the ventral tegmental area are mediated by AMPA/kainate receptors.
Am J Physiol Endocrinol Metab
; 305(11): E1367-74, 2013 Dec 01.
Article
in En
| MEDLINE
| ID: mdl-24105414
ABSTRACT
Glucagon-like peptide-1 receptor (GLP-1R) activation in the ventral tegmental area (VTA) is physiologically relevant for the control of palatable food intake. Here, we tested whether the food intake-suppressive effects of VTA GLP-1R activation are mediated by glutamatergic signaling within the VTA. Intra-VTA injections of the GLP-1R agonist exendin-4 (Ex-4) reduced palatable high-fat food intake in rats primarily by reducing meal size; these effects were mediated in part via glutamatergic AMPA/kainate but not NMDA receptor signaling. Additional behavioral data indicated that GLP-1R expressed specifically within the VTA can partially mediate the intake- and body weight-suppressive effects of systemically administered Ex-4, offering the intriguing possibility that this receptor population may be clinically relevant for food intake control. Intra-VTA Ex-4 rapidly increased tyrosine hydroxylase levels within the VTA, suggesting that GLP-1R activation modulates VTA dopaminergic signaling. Further evidence for this hypothesis was provided by electrophysiological data showing that Ex-4 increased the frequency of AMPA-mediated currents and reduced the paired/pulse ratio in VTA dopamine neurons. Together, these data provide novel mechanisms by which GLP-1R agonists in the mesolimbic reward system control for palatable food intake.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Appetite Regulation
/
Ventral Tegmental Area
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Receptors, Kainic Acid
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Receptors, Glucagon
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Receptors, AMPA
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Glucagon-Like Peptide 1
Limits:
Animals
Language:
En
Journal:
Am J Physiol Endocrinol Metab
Journal subject:
ENDOCRINOLOGIA
/
FISIOLOGIA
/
METABOLISMO
Year:
2013
Document type:
Article