The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“neurons in the VTA and/or NAc express GLP-1 (24,25), ghrelin (26,27), leptin (28,29), insulin (30), orexin (31) and melanocortin receptors (32).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [26]
In the citing paper
“Moreover, neurons in VTA and/or nucleus accumbens (NAc) express glucagon-like peptide-1 (11,12), ghrelin (13,14), leptin (15,16), insulin (17), orexin (18), and melanocortin receptors (19).”
From The Addictive Dimensionality of Obesity (2013) · cites this paper as [13]
In the citing paper
“In contrast, ghrelin action directly within the VTA appears to activate dopamine neurons, increase accumbens dopamine turnover, and increase food intake”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [1]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Ghrelin is a growth-hormone-releasing acylated peptide from stomach
Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., & Kangawa, K. (1999) · Nature · doi:10.1038/45230 · Cited by 8,479
Beaton, A. E., & Keppel, G. (1975) · American Educational Research Journal · doi:10.2307/1162588 · Cited by 5,857
Ghrelin induces adiposity in rodents
Tschöp, M., Smiley, D. L., & Heiman, M. L. (2000) · Nature · doi:10.1038/35038090 · Cited by 3,949
Self-citationA role for ghrelin in the central regulation of feeding
Nakazato, M., Murakami, N., Date, Y., Kojima, M., Matsuo, H., Kangawa, K., & Matsukura, S. (2001) · Nature · doi:10.1038/35051587 · Cited by 3,443
Watterson, K. R., Bestow, D., Gallagher, J. R., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2012) · Neurosignals · doi:10.1159/000334144 · Cited by 3,395
Plasma Ghrelin Levels after Diet-Induced Weight Loss or Gastric Bypass Surgery
Cummings, D. E., Weigle, D. S., Frayo, R. S., Breen, P. A., Marina, K., Dellinger, E. P., & Purnell, J. Q. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012908 · Cited by 2,271
A Receptor in Pituitary and Hypothalamus That Functions in Growth Hormone Release
Howard, A., Feighner, S., Cully, D., Arena, J. P., Liberator, P., Rosenblum, C., Hamelin, M., Hreniuk, D. L., Palyha, O., Anderson, J., et al. (1996) · Science · doi:10.1126/science.273.5277.974 · Cited by 2,106
Food reward: brain substrates of wanting and liking
Berridge, K. C. (1996) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(95)00033-b · Cited by 1,901
Cowley, M. A., Smith, R. G., Diano, S., Tschöp, M., Pronchuk, N., Grove, K. L., Strasburger, C. J., Bidlingmaier, M., Esterman, M., Heiman, M. L., et al. (2003) · Neuron · doi:10.1016/s0896-6273(03)00063-1 · Cited by 1,679
Self-citationOpioids excite dopamine neurons by hyperpolarization of local interneurons
Johnson, S., & North, R. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-02-00483.1992 · Cited by 1,637
Research works printed but not linked: 2
- Lacey, 1990, J. Pharmacol. Exp. Ther., 253, 395
- Small, S.V. 1968. Measurement of section thickness. In Proceedings of the 4th European Congress on Electron Microscopy. Volume 1. D.S. Bocciarelli, editor. Poliglotta Vaticana. Rome, Italy. 609–610.
Cited by
Sorted by citations
Mitochondrial ROS Signaling in Organismal Homeostasis
Shadel, G. S., & Horvath, T. L. (2015) · Cell · doi:10.1016/j.cell.2015.10.001 · Cited by 1,353
“neurons and to prevent their impairment and death in models of Parkinson’s disease (Abizaid et al., 2006; Andrews et al., 2009).”
BackgroundMüller, T. D., Nogueiras, R., Andermann, M. L., Andrews, Z. B., Anker, S. D., Argente, J., Batterham, R. L., Benoit, S. C., Bowers, C. Y., Broglio, F., et al. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.03.005 · Cited by 1,034
“Underscoring the importance of dopamine for ghrelin’s orexigenic effects is the finding that intra-VTA delivery of a ghrelin antagonist blocks the ability of parenteral ghrelin to increase feeding [239].”
Self-citationGreen, C. B., Takahashi, J. S., & Bass, J. (2008) · Cell · doi:10.1016/j.cell.2008.08.022 · Cited by 902
Obesity and addiction: Neurobiological overlaps
Volkow, N. D., Wang, G. ‐., Tomasi, D., & Baler, R. D. (2013) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01031.x · Cited by 800
“Moreover, neurons in the VTA and/or NAc express GLP-1 (24,25), ghrelin (26,27), leptin (28,29), insulin (30), orexin (31) and melanocortin receptors (32).”
BackgroundReward mechanisms in obesity: new insights and future directions
Kenny, P. J. (2011) · Neuron · doi:10.1016/j.neuron.2011.02.016 · Cited by 748
“Periods of extended access to cocaine and other drugs of abuse can drive the emergence of compulsive drug-taking behaviors in rats (Ahmed and Koob, 1998; Deroche-Gamonet et al., 2004; Vanderschuren and Everitt, 2004).”
BackgroundUCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals
Andrews, Z. B., Liu, Z.-W., Walllingford, N., Erion, D. M., Borok, E., Friedman, J. M., Tschöp, M. H., Shanabrough, M., Cline, G., Shulman, G. I., et al. (2008) · Nature · doi:10.1038/nature07181 · Cited by 710
Self-citationGhrelin Modulates Brain Activity in Areas that Control Appetitive Behavior
Malik, S., McGlone, F., Bedrossian, D., & Dagher, A. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.03.007 · Cited by 677
The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress
Lutter, M., Sakata, I., Osborne-Lawrence, S., Rovinsky, S. A., Anderson, J. G., Jung, S., Birnbaum, S., Yanagisawa, M., Elmquist, J. K., Nestler, E. J., et al. (2008) · Nature Neuroscience · doi:10.1038/nn.2139 · Cited by 644
Linking Molecules to Mood: New Insight Into the Biology of Depression
Krishnan, V., & Nestler, E. J. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.10030434 · Cited by 666
Homeostatic and hedonic signals interact in the regulation of food intake
Lutter, M., & Nestler, E. J. (2009) · The Journal of Nutrition · doi:10.3945/jn.108.097618 · Cited by 614
Steinert, R. E., Feinle-Bisset, C., Asarian, L., Horowitz, M., Beglinger, C., & Geary, N. (2017) · Physiological Reviews · doi:10.1152/physrev.00031.2014 · Cited by 578
“Insulin secretion CCK PYY(3-36) Nutrients FIGURE 7.”
BackgroundInfluentialShift Work: Disrupted Circadian Rhythms and Sleep—Implications for Health and Well-being
James, S. M., Honn, K. A., Gaddameedhi, S., & Van Dongen, H. P. A. (2017) · Current Sleep Medicine Reports · doi:10.1007/s40675-017-0071-6 · Cited by 517
Dopamine Signaling in reward-related behaviors
Baik, J. (2013) · Frontiers in Neural Circuits · doi:10.3389/fncir.2013.00152 · Cited by 568
“…www.frontiersin.org October 2013 | Volume 7 | Article 152 | 10 “fncir-07-00152” — 2013/10/9 — 21:43 — page 11 — #11 ghrelin, and blunted rebound feeding following fasting, suggesting that the DA reward circuitry is targeted by ghrelin to influence motivation for food (Abizaid et al., 2006).”
BackgroundInfluentialPYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans
Batterham, R. L., Ffytche, D. H., Rosenthal, J., Zelaya, F. O., Barker, G. J., Withers, D. J., & Williams, S. (2007) · Nature · doi:10.1038/nature06212 · Cited by 489
The cellular and molecular bases of leptin and ghrelin resistance in obesity
Cui, H., López, M., & Rahmouni, K. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.222 · Cited by 498
Gut Bacteria and Neurotransmitters
Dicks, L. M. T. (2022) · Microorganisms · doi:10.3390/microorganisms10091838 · Cited by 482
“Higher ghrelin levels are associated with elevated DA levels [67] that, in turn, send signals of satiety to the CNS [68].”
BackgroundIs dopamine a physiologically relevant mediator of feeding behavior?
Palmiter, R. D. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.06.004 · Cited by 469
Horváth, T. L., Sármán, B., García‐Cáceres, C., Enriori, P. J., Sótonyi, P., Shanabrough, M., Borók, E., Argente, J., Chowen, J. A., Pérez–Tilve, D., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004282107 · Cited by 446
“Although it is established that changes in hypothalamic synaptic plasticity of satiety-promoting melanocortin neurons can be triggered by afferent (energy balance–regulating) hormones such as leptin, estradiol, and ghrelin (12, 16), it is almost certain that the individual variability of wiring and overall flexibility…”
BackgroundSelf-citationNeuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding
Waterson, M. J., & Horváth, T. L. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.026 · Cited by 453
“, 2003), has been shown capable of altering these cells’ activity and ultimately ameliorating their impairment and death (Abizaid et al., 2006; Andrews et al., 2009), and the”
BackgroundRequirement of central ghrelin signaling for alcohol reward
Jerlhag, E., Egecioglu, E., Landgren, S., Salomé, N., Heilig, M. A., Moechars, D., Datta, R., Perrissoud, D., Dickson, S. L., & Engel, J. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812809106 · Cited by 430
“Recently we showed that, in addition to its well-described hypothalamic effects, ghrelin activates a key mesolimbic reward circuit involved in natural and druginduced reinforcement, the cholinergic–dopaminergic reward link (13–15), findings that have been corroborated and extended by others (16).”
BackgroundDickson, S. L., Shirazi, R. H., Hansson, C., Bergquist, F., Nissbrandt, H., & Skibicka, K. P. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.6326-11.2012 · Cited by 414
“Although some metabolic signals that impact on food reward target the VTA-NAc projecting neurons [for example, ghrelin (Abizaid et al., 2006; Jerlhag et al., 2007)], recent evidence suggests that some metabolic signals target nonaccumbal projecting dopamine neurons.”
BackgroundOverlapping Brain Circuits for Homeostatic and Hedonic Feeding
Rossi, M. A., & Stuber, G. D. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.09.021 · Cited by 415
“Similarly, both deprivation state and the administration of circulating satiety signals such as insulin, glucagon, or leptin can modify the rate of LHA self-stimulation (Abrahamsen et al., 1995; Balagura and Hoebel, 1967; Carr and Wolinsky, 1993; Fulton et al., 2000).”
BackgroundDeficits of mesolimbic dopamine neurotransmission in rat dietary obesity
Geiger, B. M., Haburcak, M., Avena, N. M., Moyer, M. C., Hoebel, B. G., & Pothos, E. N. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.02.007 · Cited by 403
“Other orexigenic inputs such as ghrelin and orexin have also been shown to be involved in the activation of the midbrain dopamine system (Rada et al., 1998; Helm et al., 2003; Abizaid et al., 2006; Narita et al., 2006).”
BackgroundBrain Regulation of Appetite and Satiety
Ahima, R. S., & Antwi, D. A. (2008) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2008.08.005 · Cited by 412
A link between FTO, ghrelin, and impaired brain food-cue responsivity
Karra, E., O’Daly, O., Choudhury, A. I., Yousseif, A., Millership, S. J., Neary, M. T., Scott, W. R., Chandarana, K., Manning, S., Hess, M. E., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci44403 · Cited by 396
The Addictive Dimensionality of Obesity
Volkow, N. D., Wang, G.-J., Tomasi, D., & Baler, R. D. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.12.020 · Cited by 380
“Moreover, neurons in VTA and/or nucleus accumbens (NAc) express glucagon-like peptide-1 (11,12), ghrelin (13,14), leptin (15,16), insulin (17), orexin (18), and melanocortin receptors (19).”
BackgroundGhrelin Increases the Rewarding Value of High-Fat Diet in an Orexin-Dependent Manner
Perelló, M., Sakata, I., Birnbaum, S. G., Chuang, J.-C., Osborne-Lawrence, S. L., Rovinsky, S. A., Wołoszyn, J., Yanagisawa, M., Lutter, M. L., & Zigman, J. M. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.10.030 · Cited by 385
“Developmental compensations were proposed previously to explain the finding of normal rebound hyperphagia in GHSR-knockout mice following an acute fast but blunted rebound feeding in acutely fasted wild-type mice given a GHSR antagonist (10).”
BackgroundGhrelin in the regulation of body weight and metabolism
Castañeda, T. R., Tong, J., Datta, R., Culler, M. D., & Tschöp, M. H. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.10.008 · Cited by 361
Self-citationNeurobiology of Feeding and Energy Expenditure
Gao, Q., & Horvath, T. L. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094324 · Cited by 346
“The hypothalamus is reciprocally connected to the cortex and hippocampus, the midbrain dopamine system [the ventral tegmentum (VTA)-nucleus accumbens (NAcc) pathway and the nigrostriatal dopamine projection] and brain stem autonomic regions such as the nucleus of the solitary tract (NST), area postrema (AP), dorsal mo…”
BackgroundInfluentialGhrelin mediates stress-induced food-reward behavior in mice
Chuang, J.-C., Perelló, M., Sakata, I., Osborne-Lawrence, S. L., Savitt, J. M., Lutter, M. L., & Zigman, J. M. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57660 · Cited by 347
“For instance, ghrelin induces dopamine release in the NAC and increases action potential frequency in VTA dopamine neurons (36, 40, 41).”
BackgroundInfluentialNeurobiology of food anticipatory circadian rhythms
Mistlberger, R. E. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.04.015 · Cited by 357
Central and Peripheral Regulation of Food Intake and Physical Activity: Pathways and Genes
Lenard, N. R., & Berthoud, H. (2008) · Obesity · doi:10.1038/oby.2008.511 · Cited by 338
Anisman, H., Merali, Z., & Hayley, S. P. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.01.004 · Cited by 341
“Indeed, paralleling the increased food consumption, ghrelin stimulated increased DA neuronal activity at the ventral tegmentum and influenced DA turnover at terminal sites within the nucleus accumbens (Abizaid et al., 2006).”
Ghrelin directly targets the ventral tegmental area to increase food motivation
Skibicka, K. P., Hansson, C., Álvarez-Crespo, M., Friberg, P. A., & Dickson, S. L. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.02.016 · Cited by 346
“These behavioral expressions of reward that are dependent on central ghrelin signaling are accompanied by molecular and electrophysiological evidence: ghrelin increases dopamine neuron activity in the VTA (Abizaid et al., 2006) and also increases accumbal dopamine release with an associated locomotor response (Jerlhag…”
BackgroundMethodResultInfluentialPRECLINICAL STUDY: FULL ARTICLE: Ghrelin increases intake of rewarding food in rodents
Egecioglu, E., Jerlhag, E., Salomé, N., Skibicka, K. P., Haage, D., Bohlooly‐Y, M., Andersson, D. R., Bjursell, M., Perrissoud, D., Engel, J. A., et al. (2010) · Addiction Biology · doi:10.1111/j.1369-1600.2010.00216.x · Cited by 351
“2006, 2007, 2008), a finding confirmed and extended by others (Abizaid et al. 2006).”
ResultRole of astrocytes, microglia, and tanycytes in brain control of systemic metabolism
García‐Cáceres, C., Balland, É., Prévot, V., Luquet, S. H., Woods, S. C., Koch, M., Horváth, T. L., Yi, C., Chowen, J. A., Verkhratsky, A., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0286-y · Cited by 343
Self-citationRapid sensing of circulating ghrelin by hypothalamic appetite-modifying neurons
Schaeffer, M., Langlet, F., Lafont, C., Molino, F., Hodson, D. J., Roux, T., Lamarque, L., Verdié, P., Bourrier, E., Dehouck, B., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1212137110 · Cited by 325
The Homeostatic Force of Ghrelin
Yanagi, S., Sato, T., Kangawa, K., & Nakazato, M. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.008 · Cited by 332
Broom, D. R., Batterham, R. L., King, J. A., & Stensel, D. J. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90706.2008 · Cited by 325
“This requires attention since ghrelin plays an important role in meal initiation ( 1 ) and PYY infusion, at normal postprandial concentrations, suppresses hunger in humans (3).”
BackgroundDiet-Induced Obesity Causes Ghrelin Resistance in Arcuate NPY/AgRP Neurons
Briggs, D. I., Enriori, P. J., Lemus, M. B., Cowley, M. A., & Andrews, Z. B. (2010) · Endocrinology · doi:10.1210/en.2010-0556 · Cited by 320
Self-citationVagal and hormonal gut-brain communication: from satiation to satisfaction
Berthoud, H. ‐. (2008) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2008.01104.x · Cited by 307
Gut-Brain Cross-Talk in Metabolic Control
Clemmensen, C., Müller, T. D., Woods, S. C., Berthoud, H., Seeley, R. J., & Tschöp, M. H. (2017) · Cell · doi:10.1016/j.cell.2017.01.025 · Cited by 309
“Several gut-hormones including GLP-1, PYY, and ghrelin directly affect mesolimbic dopaminergic tone and modulate food reward (Abizaid et al., 2006; Batterham et al., 2007; Dossat et al., 2011; Fulton et al., 2006).”
BackgroundSelf-citationGLP-1 and weight loss: unraveling the diverse neural circuitry
Kanoski, S. E., Hayes, M. R., & Skibicka, K. P. (2016) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00520.2015 · Cited by 290
“Alternatively, since VTA dopaminergic neurons also project to the amygdala, acute central Ex4 increases dopamine turnover in the amygdala and activation of dopamine receptors in the amygdala reduces food intake, it is likely that VTA-toamygdala dopamine projections represent an important circuit AJP-Regul Integr Comp…”
BackgroundInfluentialAndrews, Z. B., Erion, D., Beiler, R., Liu, Z.-W., Abizaid, A., Zigman, J., Elsworth, J. D., Savitt, J. M., DiMarchi, R., Tschöp, M., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3890-09.2009 · Cited by 289
“Moreover, a recent study showed that ghrelin defends against depression (Lutter et al., 2008), which is mediated by ghrelin’s action on the midbrain dopaminergic system described herein and previously (Abizaid et al., 2006; Krishnan et al., 2007).”
BackgroundResultInfluentialSelf-citationZheng, H., Lenard, N. R., Shin, A. C., & Berthoud, H. R. (2009) · International Journal of Obesity · doi:10.1038/ijo.2009.65 · Cited by 286
Kanoski, S. E., & Grill, H. J. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.09.011 · Cited by 294
“Approximately 15% to 18% of DA neurons in the VTA innervate the vCA1 and vSub, while only half as many DA neurons innervate dHP neurons (75,76).”
InfluentialFood reward, hyperphagia, and obesity
Berthoud, H.-R., Lenard, N. R., & Shin, A. C. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00028.2011 · Cited by 275
“Altered reward functions could cause obesity via increased intake of calories or fat (1), or alternatively, could result from consequences of the obese state (3), or could be a combination of both.”
BackgroundHormonal and neural mechanisms of food reward, eating behaviour and obesity
Murray, S. M., Tulloch, A. J., Gold, M. S., & Avena, N. M. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.91 · Cited by 275
Skibicka, K. P., Hansson, C., Egecioglu, E., & Dickson, S. L. (2011) · Addiction Biology · doi:10.1111/j.1369-1600.2010.00294.x · Cited by 267
Regulation of dietary choice by the decision-making circuitry
Rangel, A. (2013) · Nature Neuroscience · doi:10.1038/nn.3561 · Cited by 263
The drive to eat: comparisons and distinctions between mechanisms of food reward and drug addiction
Dileone, R., Taylor, J. R., & Picciotto, M. R. (2012) · Nature Neuroscience · doi:10.1038/nn.3202 · Cited by 255
Self-citationThe impact of gut hormones on the neural circuit of appetite and satiety: A systematic review
Zanchi, D., Depoorter, A., Egloff, L., Haller, S., Mählmann, L., Lang, U. E., Drewe, J., Beglinger, C., Schmidt, A., & Borgwardt, S. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.06.013 · Cited by 244
“MARK hypothalamus to influence several brain regions involved in the foodreward pathway, including the ventral tegmental area (VTA), nucleus accumbens, amygdala, and hippocampus (Abizaid et al., 2006; Diano et al., 2006; Nakazato et al., 2001).”
Astrocytes Control Food Intake by Inhibiting AGRP Neuron Activity via Adenosine A1 Receptors
Yang, L., Qi, Y., & Yang, Y. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.002 · Cited by 248
“For instance, the orexigenic ghrelin evokes feeding by increasing the activities of AGRP neurons through facilitating presynaptic release of glutamate (Abizaid et al., 2006; Yang et al., 2011).”
BackgroundInsulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids
Labouèbe, G., Liu, S., Dias, C., Zou, H., Wong, J. C. Y., Karunakaran, S., Clee, S. M., Phillips, A. G., Boutrel, B., & Borgland, S. L. (2013) · Nature Neuroscience · doi:10.1038/nn.3321 · Cited by 249
The role of the central ghrelin system in reward from food and chemical drugs
Dickson, S. L., Egecioglu, E., Landgren, S., Skibicka, K. P., Engel, J. A., & Jerlhag, E. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.02.017 · Cited by 248
“population of dopamine cells in this region (Abizaid et al. 2006).”
InfluentialGhrelin Gene Products and the Regulation of Food Intake and Gut Motility
Chen, C., Asakawa, A., Fujimiya, M., Lee, S., & Inui, A. (2009) · Pharmacological Reviews · doi:10.1124/pr.109.001958 · Cited by 243
Hypothalamic neuropeptides and the regulation of appetite
Parker, J., & Bloom, S. R. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.02.004 · Cited by 242
Hypothalamic control of energy balance: insights into the role of synaptic plasticity
Dietrich, M. O., & Horvath, T. L. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2012.12.005 · Cited by 227
Leptin regulates the reward value of nutrient
Domingos, A. I., Vaynshteyn, J., Voss, H. U., Ren, X., Gradinaru, V., Zang, F., Deisseroth, K. A., de Araújo, I. E., & Friedman, J. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2977 · Cited by 233
“This assay is generally applicable and can be used to establish the reward value of other nutrients and the effects of other hormone”
Ghrelin signalling and obesity: At the interface of stress, mood and food reward
Schellekens, H., Finger, B. C., Dinan, T. G., & Cryan, J. F. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.06.004 · Cited by 238
“Secondly, direct microinjection of ghrelin in VTA or NAcc was shown to strongly enhance feeding behaviour (Naleid et al., 2005; Abizaid et al., 2006).”
BackgroundBlum, K., Gardner, E., Oscar-Berman, M., & Gold, M. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212798919110 · Cited by 218
“Whereas ghrelin initially emerged as a stomach-derived hormone involved in energy balance, hunger, and meal initiation via action in food hunger-related hypothalamic circuits, it now seems clear that ghrelin also has a role in motivated reward-driven behaviors through activation of the so-called cholinergic-dopaminerg…”
BackgroundJerlhag, E., Egecioglu, E., Dickson, S. L., & Engel, J. A. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1907-7 · Cited by 219
“ghrelin also activates key CNS pathways involved in reward, that include the mesolimbic dopamine system (Abizaid et al. 2006; Jerlhag et al. 2006) and, more specifically, the cholinergic–dopaminergic reward link (Jerlhag et al.”
BackgroundInfluentialHao, J., Liu, R., Piao, W., Zhou, Q., Vollmer, T. L., Campagnolo, D. I., Xiang, R., Cava, A. L., Kaer, L. V., & Shi, F. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20092749 · Cited by 222
“Implantation was performed as previously described with some modifi cations (see Supplemental material; Abizaid et al., 2006; Hemsley et al., 2009).”
MethodHomeostasis Meets Motivation in the Battle to Control Food Intake
Ferrario, C. R., Labouèbe, G., Liu, S., Nieh, E. H., Routh, V. H., Xu, S., & O’Connor, E. C. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2338-16.2016 · Cited by 227
“…2011), whereas ghrelin increases VTA DA neuron activity and promotes food intake, effortful food seeking and favors consumption of palatable food over regular chow (Naleid et al., 2005; Abizaid et al., 2006; Zigman et al., 2006; Egecioglu et al., 2010; King et al., 2011; Skibicka et al., 2011).”
BackgroundKanoski, S. E., Fortin, S. M., Ricks, K. M., & Grill, H. J. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.07.002 · Cited by 210
Hypothalamic arcuate nucleus tyrosine hydroxylase neurons play orexigenic role in energy homeostasis
Zhang, X., & van den Pol, A. N. (2016) · Nature Neuroscience · doi:10.1038/nn.4372 · Cited by 215
Limitations in anti-obesity drug development: the critical role of hunger-promoting neurons
Dietrich, M. O., & Horváth, T. L. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3739 · Cited by 205
The extra-hypothalamic actions of ghrelin on neuronal function
Andrews, Z. B. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2010.10.001 · Cited by 199
Self-citationRole for insulin signaling in catecholaminergic neurons in control of energy homeostasis
Könner, A. C., Hess, S., Tovar, S., Mesaros, A., Sánchez-Lasheras, C., Evers, N., Verhagen, L. A. W., Brönneke, H. S., Kleinridders, A., Hampel, B., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.021 · Cited by 194
Monteleone, P., & Maj, M. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.10.021 · Cited by 199
Addiction science: Uncovering neurobiological complexity
Volkow, N. D., & Baler, R. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.05.007 · Cited by 205
“…and hormones that regulate homeostatic food signals, such as glucagon-like peptide or GLP-1 (Alhadeff et al., 2012; Rinaman, 2010), ghrelin (Abizaid et al., 2006; Jerlhag et al., 2007), leptin (Figlewicz et al., 2003; Leshan et al., 2010), insulin (Figlewicz et al., 2008), orexin (Fadel…”
BackgroundNew Insights in Anorexia Nervosa
Gorwood, P. A. P. M., Blanchet, C., Chartrel, N., Duclos, J., Déchelotte, P., Hanachi, M., Fetissov, S. O., Godart, N. T., Melchior, J., Ramoz, N., et al. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00256 · Cited by 206
“Detailed mapping of GPR103 mRNA in the brain revealed that the 26RFa receptor is expressed in the VTA, the amygdala, and the NAc (Bruzzone et al., 2007), suggesting that, in as much the same way as orexins and MCH, 26RFa may be involved in reward-based food intake.”
BackgroundInfluentialThe role of reward circuitry and food addiction in the obesity epidemic: An update
Leigh, S.-J., & Morris, M. J. (2018) · Biological Psychology · doi:10.1016/j.biopsycho.2016.12.013 · Cited by 191
Ferrini, F., Salio, C., Lossi, L., & Merighi, A. (2009) · Current Neuropharmacology · doi:10.2174/157015909787602779 · Cited by 198
“The effect of ghrelin in midbrain has been recently described in ventral tegmental area (VTA) and nucleus accumbens (Nacc) [1, 104].”
Obesity: Pathophysiology and Intervention
Zhang, Y., Liu, J., Yao, J., Ji, G., Qian, L., Wang, J., Zhang, G., Tian, J., Nie, Y., Zhang, Y., et al. (2014) · Nutrients · doi:10.3390/nu6115153 · Cited by 204
“Dopamine is a neurotransmitter critical for reward processing, motivation, and positive behavior reinforcement [31,61], and plays an important role in the reward-saliency circuit.”
BackgroundThe central GLP-1: implications for food and drug reward
Skibicka, K. P. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00181 · Cited by 188
Obesity: Current and potential pharmacotherapeutics and targets
Narayanaswami, V., & Dwoskin, L. P. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.10.015 · Cited by 188
“…intra-VTA infusions of GHSR antagonist, BIM28163 (4-[[(2S)-2-[[(2R)-2-[[(2R)-3-(1-benzothiophene-3-yl)-2-(piperidine-3carbonylamino)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3phenylpropanoyl]amino]piperidine-4-carboxamide; 0.5 μg/0.5 μl) given 1 h prior to ghrelin (Abizaid et al., 2006).”
InfluentialGhrelin Acts as an Interface between Physiological State and Phasic Dopamine Signaling
Cone, J. J., McCutcheon, J. E., & Roitman, M. F. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.4404-13.2014 · Cited by 187
“Ghrelin receptors are present on VTA dopamine neurons (Abizaid et al., 2006) and previous evidence suggests that administration of ghrelin into the VTA increases dopamine in the NAc shell (Jerlhag et al., 2007).”
BackgroundInfluentialJerlhag, E. (2008) · Addiction Biology · doi:10.1111/j.1369-1600.2008.00125.x · Cited by 186
“Additionally, ventral tegmental administration of ghrelin increases food intake in mice, implying that ghrelin may also regulate elemental feeding behaviour via activation of the mesolimbic DA system (Naleid et al. 2005; Abizaid et al. 2006).”
BackgroundResultInfluentialSimultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure
Pfluger, P. T., Kirchner, H., Günnel, S., Schrott, B., Pérez–Tilve, D., Fu, S., Benoit, S. C., Horváth, T. L., Joost, H., Wortley, K. E., et al. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00321.2007 · Cited by 184
Self-citationCircadian Rhythms and Hormonal Homeostasis: Pathophysiological Implications
Gnocchi, D., & Bruscalupi, G. (2017) · Biology · doi:10.3390/biology6010010 · Cited by 193
Tauber, M., & Höybye, C. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00002-4 · Cited by 187
From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation
Howick, K., Griffin, B. T., Cryan, J. F., & Schellekens, H. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020273 · Cited by 188
“Central ghrelin administration recruits dopaminergic neurons in the VTA and results in an elevated dopaminergic tone in the nucleus accumbens (NAcc) of mice, while more targeted intra-VTA administration robustly increases the intake of both standard chow [17,345] and palatable food [265,346].”
BackgroundCircadian rhythms and mood regulation: insights from pre-clinical models
McClung, C. A. (2011) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2011.07.008 · Cited by 169
“enhance the firing of VTA dopamine neurons (Abizaid et al. 2006).”
BackgroundMetabolic hormones, dopamine circuits, and feeding
Narayanan, N. S., Guarnieri, D. J., & Dileone, R. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.10.004 · Cited by 182
“Considering this broad literature, it is difficult to really specify the role of mesolimbic dopamine in free feeding: whereas mesolimbic dopamine neuron depletions do not specifically impact free feeding, neurochemical manipulations of the VTA and NAc [25;26] as well as infusions of opioid, leptin or ghrelin directly…”
BackgroundInfluentialHedonic and incentive signals for body weight control
Egecioglu, E., Skibicka, K. P., Hansson, C., Álvarez-Crespo, M., Friberg, P. A., Jerlhag, E., Engel, J. A., & Dickson, S. L. (2011) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-011-9166-4 · Cited by 192
“This link includes a cholinergic afferent projection from the LDTg onto the VTA dopamine cells.”
BackgroundInfluentialAn update on the connections of the ventral mesencephalic dopaminergic complex
Yetnikoff, L., Lavezzi, H. N., Reichard, R. A., & Zahm, D. S. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.04.010 · Cited by 189
“…that the sensitivity with which neurons in the midbrain DA complex respond to physiological stimuli is dependent on concentrations of circulating hormones (e.g., Deroche et al., 1995; Rougé-Pont et al., 1995) and peptides (e.g., Abizaid et al., 2006; Fulton et al., 2006; Hommel et al., 2006).”
BackgroundGhrelin Signalling on Food Reward: A Salient Link Between the Gut and the Mesolimbic System
Perelló, M., & Dickson, S. L. (2014) · Journal of Neuroendocrinology · doi:10.1111/jne.12236 · Cited by 177
Brain circuits regulating energy homeostasis
Abizaid, A. B., & Horváth, T. L. (2008) · Regulatory Peptides · doi:10.1016/j.regpep.2007.10.006 · Cited by 171
Self-citationBrain regulation of energy balance and body weight
Rui, L. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-013-9261-9 · Cited by 168
“In contrast, ghrelin directly binds to neurons in the VTA, increasing dopamine transmission from VTA to NAc neurons [184].”
BackgroundThe brain’s reward system in health and disease
Lewis, R. G., Florio, E., Punzo, D., & Borrelli, E. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-81147-1_4 · Cited by 170
“Clock is expressed in the VTA and NAcc and has been implicated in modulating reward processing.”
BackgroundInfluentialÁlvarez-Crespo, M., Skibicka, K. P., Farkas, I., Molnár, C. S., Egecioglu, E., Hrabovszky, E., Liposits, Z., & Dickson, S. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046321 · Cited by 169
“For electrophysiological studies, the selected dose was 4 mM for ghrelin [11,32] and 10 mM for”
MethodImaging of Brain Dopamine Pathways
Wang, G., Volkow, N. D., Thanos, P. K., & Fowler, J. S. (2009) · Journal of Addiction Medicine · doi:10.1097/adm.0b013e31819a86f7 · Cited by 176
Palatability Can Drive Feeding Independent of AgRP Neurons
Denis, R. G. P., Joly-Amado, A., Webber, E., Langlet, F., Schaeffer, M., Padilla, S. L., Cansell, C., Dehouck, B., Castel, J., Delbès, A.-S., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.07.011 · Cited by 164
“Although the direct access of circulating hormones such as ghrelin or leptin to these structures lying away from the blood brain barrier (BBB) entry point is still a matter of debate, injection of these hormones into the ventral tegmental area (VTA) or parabrachial nucleus (PBN) can inhibit feeding (Abizaid et al., 20…”
BackgroundCircadian adaptations to meal timing: neuroendocrine mechanisms
Patton, D. F., & Mistlberger, R. E. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00185 · Cited by 176
“Mc3R receptors are predominantly expressed in hypothalamic and limbic structures, with high levels in areas implicated in feeding and reward (VMH and VTA) (Roselli-Rehfuss et al., 1993), while Mc4R are more widely distributed within the brain.”
BackgroundInfluentialOswal, A., & Yeo, G. S. H. (2009) · Obesity · doi:10.1038/oby.2009.228 · Cited by 170
“Although this re-wring of synaptic inputs occurs over a much shorter time course than the observed change in feeding behavior, its importance to normal energy homeostasis is highlighted by the fact that another appetite regulatory hormone, ghrelin, has a similar effect (79).”
BackgroundFulton, S. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.10.003 · Cited by 172
“Illustrating the direct action of ghrelin on VTA DA neurons, Abizaid and coworkers demonstrated that ghrelin binds to VTA cells and increases DA firing [3].”
BackgroundStrasser, F., Lutz, T. A., Maeder, M. T., Thuerlimann, B., Bueche, D., Tschöp, M. H., Kaufmann, K., Holst, B., Brändle, M., von Moos, R., et al. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604148 · Cited by 161
Self-citationLoeber, S., Grosshans, M., Herpertz, S., Kiefer, F., & Herpertz, S. C. (2013) · Appetite · doi:10.1016/j.appet.2013.07.008 · Cited by 159
“Thus, ghrelin receptors are located in dopaminergic neurons within the ventral tegmentum of the midbrain and stimulate the firing rate of neurons projecting to the nucleus accumbens (Abizaid et al. 2006).”
BackgroundRouach, V., Bloch, M., Rosenberg, N., Gilad, S., Limor, R., Stern, N., & Greenman, Y. (2007) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2007.04.010 · Cited by 159
“Ghrelin directly activates dopaminergic neurons in the VTA and increases synapse formation and dopamine turnover in the nucleus accumbens (Abizaid et al., 2006).”
Metadata
- Authors
- Abizaid, A., Liu, Z.-W., Andrews, Z. B., Shanabrough, M., Borok, E., Elsworth, J. D., Roth, R. H., Sleeman, M. W., Picciotto, M. R., Tschöp, M. H., Gao, X.-B., & Horvath, T. L.
- Affiliations
- Yale University (US)
- Regeneron (United States) (US)
- University of Cincinnati (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2006-12-01
- Volume
- 116
- Issue
- 12
- Pages
- 3229-3239
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2086950122
- Cited by
- 984
- References
- 58
- Citations by year
- 2026: 23 · 2025: 33 · 2024: 31 · 2023: 34 · 2022: 46 · 2021: 53 · 2020: 44 · 2019: 40 · 2018: 56 · 2017: 66 · 2016: 51 · 2015: 57 · 2014: 60 · 2013: 73 · 2012: 78
- FWCI
- 15.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Yale University
- Ipsen
- National Institutes of Health (5r01mh057483-13, DK056863)
- Raymond and Beverly Sackler Institute for Biological, Physical and Engineering Sciences, Yale University
- National Institute on Alcohol Abuse and Alcoholism (P50AA015632)
- National Institute on Aging (R01AG022880, AG-022880)
- National Institute of Mental Health (R01-MH057483, R01MH014092, MH014092, MH057483, R37MH014092)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK070723, DK-056863, DK-069987, DK 060711, DK 070723, P01DK056863, DK074386, R01DK069987, R01DK074386, R01DK060711)
- National Institute of Neurological Disorders and Stroke (R01NS041725, NS-041725)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- ghrelin, ventral tegmental area, dopaminergic neurons, nucleus accumbens, synaptic plasticity, feeding behavior, appetite, mesolimbic reward circuitry, energy metabolism
- MeSH terms
- Action Potentials, Animals, Appetite, Dopamine, Fluorescent Antibody Technique, Male, Mesencephalon, Mice, Inbred C57BL, Neurons, Nucleus Accumbens, Time Factors, Rats, Sprague-Dawley, Ventral Tegmental Area, Mice, Knockout, Patch-Clamp Techniques, Peptide Hormones, Receptors, G-Protein-Coupled, Mice, Rats, Ghrelin, Receptors, Ghrelin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
