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Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite
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Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite
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Journal Article
Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite
2006
Overview
The gut hormone ghrelin targets the brain to promote food intake and adiposity. The ghrelin receptor growth hormone secretagogue 1 receptor (GHSR) is present in hypothalamic centers controlling energy metabolism as well as in the ventral tegmental area (VTA), a region important for motivational aspects of multiple behaviors, including feeding. Here we show that in mice and rats, ghrelin bound to neurons of the VTA, where it triggered increased dopamine neuronal activity, synapse formation, and dopamine turnover in the nucleus accumbens in a GHSR-dependent manner. Direct VTA administration of ghrelin also triggered feeding, while intra-VTA delivery of a selective GHSR antagonist blocked the orexigenic effect of circulating ghrelin and blunted rebound feeding following fasting. In addition, ghrelin- and GHSR-deficient mice showed attenuated feeding responses to restricted feeding schedules. Taken together, these data suggest that the mesolimbic reward circuitry is targeted by peripheral ghrelin to influence physiological mechanisms related to feeding.
Publisher
American Society for Clinical Investigation
Subject
Action Potentials - drug effects
/ Animals
/ Dopamine
/ Fluorescent Antibody Technique - methods
/ Food
/ Ghrelin
/ Labeling
/ Male
/ Mesencephalon - drug effects
/ Mice
/ Nucleus Accumbens - cytology
/ Nucleus Accumbens - drug effects
/ Nucleus Accumbens - metabolism
/ Peptide Hormones - metabolism
/ Peptide Hormones - pharmacology
/ Rats
/ Receptors, G-Protein-Coupled - metabolism
/ Ventral Tegmental Area - cytology
