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- Title
Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite.
- Authors
Abizaid, Alfonso; Zhong-Wu Liu; Andrews, Zane B.; Shanabrough, Marya; Borok, Erzsebet; Elsworth, John D.; Roth, Robert H.; Sleeman, Mark W.; Picciotto, Marina R.; Tschöp, Matthias H.; Xiao-Bing Gao; Horvath, Tamas L.; Liu, Zhong-Wu; Tschöp, Matthias H; Gao, Xiao-Bing
- Abstract
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.
- Subjects
GHRELIN; GASTROINTESTINAL hormones; INGESTION; OBESITY; ENERGY metabolism; DOPAMINERGIC neurons; NEURAL physiology; ACTION potentials; ANIMAL experimentation; APPETITE; BASAL ganglia; BRAIN stem; CELL receptors; COMPARATIVE studies; CYTOLOGICAL techniques; DOPAMINE; FLUORESCENT antibody technique; RESEARCH methodology; MEDICAL cooperation; MICE; NEURONS; PEPTIDE hormones; RATS; RESEARCH; TIME; EVALUATION research
- Publication
Journal of Clinical Investigation, 2006, Vol 116, Issue 12, p3229
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI29867