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Publication : Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite.

First Author  Abizaid A Year  2006
Journal  J Clin Invest Volume  116
Issue  12 Pages  3229-39
PubMed ID  17060947 Mgi Jnum  J:117370
Mgi Id  MGI:3696310 Doi  10.1172/JCI29867
Citation  Abizaid A, et al. (2006) Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. J Clin Invest 116(12):3229-39
abstractText  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.
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