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Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite
Alfonso Abizaid, … , Xiao-Bing Gao, Tamas L. Horvath
Alfonso Abizaid, … , Xiao-Bing Gao, Tamas L. Horvath
Published December 1, 2006
Citation Information: J Clin Invest. 2006;116(12):3229-3239. https://doi.org/10.1172/JCI29867.
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Research Article Metabolism Article has an altmetric score of 12

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

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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.

Authors

Alfonso Abizaid, Zhong-Wu Liu, Zane B. Andrews, Marya Shanabrough, Erzsebet Borok, John D. Elsworth, Robert H. Roth, Mark W. Sleeman, Marina R. Picciotto, Matthias H. Tschöp, Xiao-Bing Gao, Tamas L. Horvath

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Figure 5

Ghrelin alters dopamine turnover and feeding via the VTA.

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Ghrelin alters dopamine turnover and feeding via the VTA.
(A) Peripheral...
(A) Peripheral ghrelin treatment (1 mg/kg) was effective in increasing DA turnover in the nucleus accumbens of rats (n = 12). (B) Ghrelin treatment (30 or 100 μg) of ghrelin-deficient mice increased DA turnover in the ventral striatum in a dose-dependent manner compared with saline-treated mice. Conversely, ghrelin induced no alterations in DA turnover of the nucleus accumbens in Ghsr–/– mice (n = 5 per treatment). (C) VTA ghrelin infusions (0.5 μg in 0.5 μl saline) significantly increased food intake in rats compared with saline infusions or with infusions at sites adjacent to, but not in, the VTA (Sham). (D) Ghrelin (5 μg in 0.1 ml saline) injected i.p. increased food intake compared with saline-injected rats, an effect blocked by BIM28163 infusion (0.5 ng in 0.5 μl saline) directly into the VTA. (E and F) Rebound feeding 6 hours after fasting was significantly attenuated in mice treated with BIM12863 (1 nM/d) infused into the VTA at 0.25 μl/h (E). This effect was statistically significant only during the first hour after food was reintroduced (F). (G and H) Six-hour food intake in ghrelin- (G) and GHSR-deficient (H) mice under a restricted feeding schedule. Both ghrelin- and GHSR-deficient mice showed attenuated feeding responses after repeated overnight fasts. †P < 0.05 versus respective controls. #P < 0.05 versus saline/saline and BIM28163/saline treatment groups; ##P < 0.05 versus saline/ghrelin treatment group.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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