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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.
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“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]
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Cites
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BackgroundGhrelin O-acyltransferase knockout mice show resistance to obesity when fed high-sucrose diet
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Ghosh‐Swaby, O. R., Reichelt, A. C., Sheppard, P. A. S., Davies, J. S., Bussey, T. J., & Saksida, L. M. (2022) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2022.101009 · Cited by 25
GABA Keeps Up an Appetite for Life
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BackgroundMethodSelf-citationCircannual changes in stress and feeding hormones and their effect on food-seeking behaviors
Cahill, S. P., Tuplin, E. W. N., & Holahan, M. R. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00140 · Cited by 25
“As such, blockade of glutamatergic signaling following intra-VTA administration of the NMDAr antagonist AP5, blocked ghrelin-induced DA output in the Acb along with ghrelin-induced locomotor elevation (Jerlhag et al., 2011a).”
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The (dys)regulation of energy storage in obesity
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Role of Ghrelin in the Pathophysiology of Eating Disorders
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“Ghrelin administration directly in either the VTA or the NAc was found to have an orexigenic effect.([80,86]) Furthermore, ghrelin specifically enhances the intake of palatable food,([87]) which is dependent on VTA ghrelin signalling.”
BackgroundInfluentialLinking drug and food addiction: an overview of the shared neural circuits and behavioral phenotype
Passeri, A., Municchi, D., Cavalieri, G., Babicola, L., Ventura, R., & Segni, M. D. (2023) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2023.1240748 · Cited by 32
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“…operant behavioural response learned during hunger (fasting) [10,30]; 2) ghrelin increases food intake, motivation and dopamine neural circuits [16,31 e 33]; 3) ghrelin supresses energy expenditure and lipid utilisation [34,35]; and 4) ghrelin reduces anxiety-like behaviour and increases…”
BackgroundInfluentialSelf-citationHormonal regulation of the arcuate nucleus melanocortin system
Coppola, A. M. (2007) · Frontiers in bioscience · doi:10.2741/2331 · Cited by 24
“Insulin has also been shown to decrease pleasurable responses to food through the limbic system, nucleus accumbens and VTA (44).”
BackgroundAcylation type determines ghrelin's effects on energy homeostasis in rodents.
Heppner, K., Chaudhary, N., Müller, T., Kirchner, H., Habegger, K., Ottaway, N., Smiley, D., DiMarchi, R., Hofmann, S., Woods, S. C., et al. (2012) · Endocrinology · doi:10.1210/en.2012-1194 · Cited by 23
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Control of Appetite and Food Preference by NMDA Receptor and Its Co-Agonist d-Serine
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“for GLP-1 [23], ghrelin [24,25], leptin [26,27], insulin [26], and orexin [28].”
BackgroundHungry to gamble? Ghrelin as a predictor of persistent gambling in the face of loss
Sztainert, T., Hay, R. E., Wohl, M. J. A., & Abizaid, A. B. (2018) · Biological Psychology · doi:10.1016/j.biopsycho.2018.10.011 · Cited by 26
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“This finding is in agreement with previously reported ghrelin-inducedincreases in accumbal dopamine turnover (Abizaid et al. 2006) and expression of tyrosine hydroxlase mRNA in midbrain dopamine neurons (Andrews et al. 2009).”
Early life disruption to the ghrelin system with over-eating is resolved in adulthood in male rats
Sominsky, L., Ziko, I., Nguyen, T.-X., Andrews, Z. B., & Spencer, S. J. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.09.023 · Cited by 23
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Central manipulation of dopamine receptors attenuates the orexigenic action of ghrelin
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Ghrelin stimulates synaptic formation in cultured cortical networks in a dose-dependent manner
Stoyanova, I. I., le Feber, J., & Rutten, W. L. C. (2013) · Regulatory Peptides · doi:10.1016/j.regpep.2013.07.004 · Cited by 23
“of ghrelin on synaptogenesis in dissociated cortical neurons is mediated via GHSR1, as was shown in the ventral thalamic area and substantia nigra of mice and rat [43].”
BackgroundPatterson, Z. R., Parno, T., Isaacs, A. M., & Abizaid, A. B. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00167 · Cited by 22
Self-citationChebani, Y., Marion, C., Zizzari, P., Chettab, K., Pastor, M., Korostelev, M., Gény, D., Epelbaum, J., Tolle, V., Morisset‐Lopez, S., et al. (2016) · Science Signaling · doi:10.1126/scisignal.aae0374 · Cited by 24
“Ghrelin is a pleiotropic hormone secreted by the stomach (1) that promotes food-seeking behaviors and a positive energy balance by means of several central mechanisms involving hedonic (2-4) and energy homeostasis circuits (5-8).”
Sharpe, M. J., Clemens, K. J., Morris, M. J., & Westbrook, R. F. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.287 · Cited by 27
“The ghrelin receptor (GHS-R1a) is abundant in mesolimbic circuitry and ghrelin is thought to have a role in the ingestion elicited by hedonically attractive foods (Abizaid et al, 2006; Schellekens et al 2013).”
BackgroundCuesto, G., Everaerts, C., León, L. G., & Acebes, Á. (2017) · Journal of Neurogenetics · doi:10.1080/01677063.2017.1353092 · Cited by 23
“In rodents, ghrelin injection increases food intake and triggers dopamine release (Abizaid et al., 2006; Kawahara et al., 2009).”
BackgroundModeling the effects of motivation on choice and learning in the basal ganglia
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“More specifically, the orexigenic hormone ghrelin increases dopamine release [57], whereas the anorexigenic hormone leptin decreases dopamine release from the midbrain [58].”
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Horváth, T. L., Erion, D. M., Elsworth, J. D., Roth, R. H., Shulman, G. I., & Andrews, Z. B. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.03.005 · Cited by 23
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Ghrelin's effects on food motivation in rats are not limited to palatable foods
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“, on dopaminergic and also GABAergic neurons) [35,39]; thus, their antagonism could affect the relevant neural sensitivity, including the dopamine-independent mechanisms.”
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“Ghrelin has been shown to regulate brain functions such as modulation of cognitive processes, not only in the hypothalamus but also in other brain areas with stimulatory effect on memory retention through promotion of synaptic plasticity [8], and generation of long-term potentiation [21,22,23].”
BackgroundDepression and metabolism: linking changes in leptin and ghrelin to mood
Lutter, M. L., & Elmquist, J. K. (2009) · F1000 Biology Reports · doi:10.3410/b1-63 · Cited by 22
du Hoffmann, J., & Nicola, S. M. (2016) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2016.00144 · Cited by 24
Physiology, pathophysiology and therapeutic implications of enteroendocrine control of food intake
Elliott, J. A., Reynolds, J. V., le Roux, C. W., & Docherty, N. G. (2016) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2016.1245140 · Cited by 22
“both dopaminergic and GABAergic neurons [94].”
Skov, L. J., Jensen, M. G., Christiansen, S., Ratner, C., Woldbye, D. P. D., & Holst, B. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18050914 · Cited by 22
“Additionally, intra-VTA administration of a Ghr-R antagonist attenuates the ability of peripheral ghrelin to increase food intake, highlighting the importance of the mesolimbic system for the orexigenic effects of ghrelin [2].”
BackgroundOkumura, T., Nozu, T., Kumei, S., Takakusaki, K., & Ohhira, M. (2018) · Brain Research · doi:10.1016/j.brainres.2018.02.024 · Cited by 22
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“The prevention of increases in food intake by peripheral ghrelin administration when a GHSR antagonist (BIM28163) is administered into the ventral tegmental area in laboratory rats (Abizaid et al., 2006) suggests that activation of GHSRs in the VTA alone may be necessary for peripheral ghrelin-induced increases in foo…”
BackgroundBarrile, F., Cassano, D., Fernández, G., Francesco, P. N. D., Reynaldo, M. B., Cantel, S., Fehrentz, J., Donato, J., Schiöth, H. B., Zigman, J. M., et al. (2023) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2023.106333 · Cited by 21
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Self-citationObesity and Brain Positron Emission Tomography
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“More recently ghrelin has been shown to modulate the activity of the dopaminergic neurons of the ventral tegmental area (VTA) and substantia niagra and has been shown to be involved in reward seeking behavior such as alcohol abuse, cocaine, or intake of palatable food (Abizaid et al., 2006; Diano et al., 2006; Jerlhag…”
BackgroundGhrelin and aggressive behaviours—Evidence from preclinical and human genetic studies
Vestlund, J., Jörnulf, J. W., Hovey, D., Lundström, S., Lichtenstein, P., Anckarsäter, H. S., Studer, E., Suchankova, P., Westberg, L., & Jerlhag, E. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.02.020 · Cited by 21
“During recent years a modulatory role of ghrelin in reward processing, via activation of reward related areas, has been established in both rodents and humans (Abizaid et al., 2006; Jerlhag, 2008; Jerlhag et al., 2006; Malik et al., 2008; Muller et al., 2015; Quarta et al., 2009; Wellman et al., 2012).”
Central administration of ghrelin induces conditioned avoidance in rodents
Schéle, E., Cook, C. P., May, M. V. L., Bake, T., Luckman, S. M., & Dickson, S. L. (2017) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2017.05.001 · Cited by 19
“GHS-R1A is also abundant in reward-linked brain regions such as the ventral tegmental area (VTA) (Abizaid et al., 2006; Zigman et al., 2006), and has been found to be co-localized with a subpopulation of dopaminergic neurons in this area (Abizaid et al.”
InfluentialKim, J., Nakajima, K., Oomura, Y., Wayner, M. J., & Sasaki, K. (2008) · Peptides · doi:10.1016/j.peptides.2008.12.004 · Cited by 21
“In vitro whole cell patch clamp recording studies also indicate that ghrelin excites ventral tegmental dopaminergic neurons [1], and depolarizes dissociated neurons of the subfornical organ and tuberomammillary nucleus [2,35].”
BackgroundNeuroendocrine Peptides of the Gut and Their Role in the Regulation of Food Intake
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A randomized controlled experimental medicine study of ghrelin in value-based decision making
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“Peripheral ghrelin has been proposed to promote appetite and increase the reward value of food in part by potentiating meso-limbic DA signaling (25–28).”
Sárvári, M., Kocsis, P., Deli, L., Gajári, D., Dávid, S., Pozsgay, Z., Hegedűs, N., Tihanyi, K., & Liposits, Z. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097651 · Cited by 19
“GHS-R1A mRNA has been detected within A10 dopaminergic neurons and cholecystokinin-immunoreactive neurons of the VTA [4].”
BackgroundInfluentialRecent Advances in the Neurobiology of Altered Motivation Following Bariatric Surgery
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The Potential Roles of Ghrelin in Metabolic Syndrome and Secondary Symptoms of Alzheimer’s Disease
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“Notably, targeted injections of the GHSR antagonist BIM28163 in this region block the orexigenic actions of peripherally administered ghrelin (Abizaid et al., 2006).”
BackgroundInfluentialLeptin action in the midbrain: From reward to stress
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“In recent years there has been tremendous progress in deciphering how the homeostatic system in the hypothalamus modulates appetite and metabolism and thereby regulates body weight (Abizaid et al., 2006; Morton et al., 2006; Karatsoreos et al., 2013).”
BackgroundThe interoceptive origin of reinforcement learning
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“…projection of dopamine from the VTA to the nucleus accumbens, stimulating food-seeking behavior, meal intake and, if given centrally, locomotion in a GHS-R1α-dependent manner (Abizaid et al., 2006; Cornejo et al., 2018; Jerlhag et al., 2007, 2012; Quarta et al., 2009; Skibicka et al., 2011, 2012).”
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Ghrelin regulates cell cycle-related gene expression in cultured hippocampal neural stem cells
Chung, H., & Park, S. (2016) · Journal of Endocrinology · doi:10.1530/joe-16-0126 · Cited by 19
Pluripotent Stem Cells for Modelling and Cell Therapy of Parkinson’s Disease
Lebedeva, O. S., & Lagarkova, M. A. (2018) · Biochemistry (Moscow) · doi:10.1134/s0006297918090067 · Cited by 19
Ghrelin in neuroendocrine tumors
Vu, J. P., Wang, H. S., Germano, P. M., & Pisegna, J. R. (2011) · Peptides · doi:10.1016/j.peptides.2011.10.006 · Cited by 18
“Gastrin, a specific tumor marker in patients with gastrinoma, has also been found to have a relatively low sensitivity and specificity for detecting either an increase in gastrinoma size or tumor stabilization over time [1,69].”
BackgroundA mathematical model of food intake.
Chudtong, M., & Gaetano, A. D. (2021) · Mathematical biosciences and engineering : MBE · doi:10.3934/mbe.2021067 · Cited by 18
“Of importance in connection with the present work is the finding that dopamine signaling and the secretion of dopamine can be activated by ghrelin [31, 45], with the result that feeding is promoted.”
BackgroundGross, J., Kim, D. W., Zhou, Y., Jansen, D. J., Slosky, L. M., Clark, N. B., Ray, C., Hu, X., Southall, N. T., Wang, A., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2112397119 · Cited by 18
Jang, J. K., Kim, W. Y., Cho, B. R., Lee, J. W., & Kim, J. (2017) · Addiction Biology · doi:10.1111/adb.12533 · Cited by 18
“disappeared when glutamatergic neurotransmission was blocked, while they were intact when GABAergic neurotransmission was blocked (Abizaid et al. 2006), suggesting that glutamate system can be a target to be activated by ghrelin.”
BackgroundCook, J. B., Hendrickson, L. M., Garwood, G. M., Toungate, K. M., Nania, C. V., & Morikawa, H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0183685 · Cited by 18
Adipocytokines and ghrelin level of bipolar patients from manic episode to euthymic episode
Tunçel, Ö. K., Sarísoy, G., Bilgici, B., Pazvantoğlu, O., Çetin, E., & Tunçel, E. K. (2017) · Nordic Journal of Psychiatry · doi:10.1080/08039488.2017.1402953 · Cited by 18
“However, direct administration of ghrelin into the ventricular tegmental area (VTA) stimulates the mesolimbic dopamine system and food intake [20].”
BackgroundA review of the neurobiology of obesity and the available pharmacotherapies
Subramaniapillai, M., & McIntyre, R. S. (2017) · CNS Spectrums · doi:10.1017/s1092852917000839 · Cited by 18
“Ghrelin receptors are also found in the VTA and stimulate dopaminergic neurons in the NAc.(14) In preclinical studies, inhibition of the ghrelin receptors has led to a decrease in reward-associated food consumption.”
BackgroundInfluentialCharalambous, C., Havlickova, T., Lapka, M., Puskina, N., Šlamberová, R., Kuchař, M., & Šustková-Fišerová, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052397 · Cited by 18
“It should be taken into consideration that ghrelin has its own reinforcing properties [76,77].”
BackgroundÍbias, J., Miguéns, M., Rio, D. D., Valladolid‐Acebes, I., Stucchi, P., Ambrosio, E., Martín, M. E., Morales, L., Ruiz‐Gayo, M., & Olmo, N. D. (2015) · European Journal of Nutrition · doi:10.1007/s00394-015-0980-4 · Cited by 19
Neuroendocrine and metabolic activities of ghrelin gene products
Baragli, A., Lanfranco, F., Allasia, S., Granata, R., & Ghigo, E. (2011) · Peptides · doi:10.1016/j.peptides.2011.10.024 · Cited by 18
Mutschler, J., Graf, N., Spanaus, K. S., Wulf Rössler, A., Hergan, K., Binkert, C. A., & Gutzeit, A. (2012) · PubMed · doi:10.5167/uzh-64365 · Cited by 18
“However, ghrelin, an orexigenic hormone, suggested to be also involved in mesolimbic dopaminergic pathways (Abizaid et al. 2006), which play a central role in the development and maintenance of addictive disorders, such as nicotine addiction, has not been investigated so far.”
Background“Sibling” battle or harmony: Crosstalk between nesfatin-1 and ghrelin
Chen, X., Dong, J., Jiao, Q., Du, X., Bi, M., & Jiang, H. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04193-6 · Cited by 17
“Ghrelin reversed all above effects [78, 79], moreover, blockage of D-Rs in the NAc attenuated the effect of ghrelin in the VTA [80].”
BackgroundKoopmann, A., Lippmann, K. I., Schuster, R., Reinhard, I., Bach, P., Weil, G., Rietschel, M., Witt, S. H., Wiedemann, K., & Kiefer, F. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.08.005 · Cited by 17
Mancini, M., Patel, J. C., Affinati, A. H., Witkovsky, P., & Rice, M. E. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.0238-22.2022 · Cited by 18
Dopamine-inhibited POMCDrd2+ neurons in the ARC acutely regulate feeding and body temperature
Gaziano, I., Corneliussen, S., Biglari, N., Neuhaus, R., Shen, L., Sotelo-Hitschfeld, T., Klemm, P., Steuernagel, L., Solís, A. J. D., Chen, W., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.162753 · Cited by 19
Voluntary exercise is motivated by ghrelin, possibly related to the central reward circuit
Mifune, H., Tajiri, Y., Sakai, Y., Kawahara, Y., Hara, K., Sato, T., Nishi, Y., Nishi, A., Mitsuzono, R., Kakuma, T., et al. (2019) · Journal of Endocrinology · doi:10.1530/joe-19-0213 · Cited by 17
“…the central administration of ghrelin directly to the VTA has been shown to be associated with the release of dopamine and motivational feeding (Abizaid et al. 2006, Jerlhag et al. 2007, Cone et al. 2015), few reports have demonstrated that the systemic administration of ghrelin can affect the…”
Involvement of Ghrelin Dynamics in Stress-Induced Eating Disorder: Effects of Sex and Aging
Yamada, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111695 · Cited by 20
Colvin, K. J., Killen, H. S., Kanter, M. J., Halperin, M. C., Engel, L., Dickinson, M., Fimmel, A. I., Holland, J. G., & Currie, P. J. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113726 · Cited by 16
Tachykinin-1 in the Central Nervous System Regulates Adiposity in Rodents
Trivedi, C. J., Shan, X., Tung, Y. L., Kabra, D. G., Holland, J., Amburgy, S. E., Heppner, K. M., Kirchner, H., Yeo, G. S. H., & Pérez–Tilve, D. (2015) · Endocrinology · doi:10.1210/en.2014-1781 · Cited by 17
Distinctive striatal dopamine signaling after dieting and gastric bypass
Hankir, M. K., Ashrafian, H., Hesse, S., Horstmann, A., & Fenske, W. K. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.03.005 · Cited by 16
Hunger improves reinforcement-driven but not planned action
van Swieten, M. M. H., Bogacz, R., & Manohar, S. (2021) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-021-00921-w · Cited by 17
“In particular, leptin inhibits and ghrelin activates dopaminergic neurons in the ventral tegmental area, and could therefore modulate learning and decision-making via the mesolimbic pathway (Abizaid et al., 2006; Figlewicz et al., 2007; Hommel et al., 2006).”
Terrill, S. J., Wall, K. D., Medina, N. D., Maske, C. B., & Williams, D. L. (2018) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00339.2017 · Cited by 16
“More recent studies have demonstrated that, in the nucleus accumbens, ventral tegmental area, and hippocampus, ghrelin promotes food intake, and this effect appears to be driven by an increase in motivation (1, 14, 15, 19, 21).”
BackgroundStutz, B., Nasrallah, C. M., Nigro, M., Curry, D. W., Liu, Z.-W., Gao, X., Elsworth, J. D., Mintz, L., & Horváth, T. L. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.02.005 · Cited by 15
“Whole-body GHSR KO mice were also available in our laboratory [41].”
MethodSelf-citationGhrelin signalling within the rat nucleus accumbens and skilled reach foraging
Vestlund, J., Bergquist, F., Eckernäs, D., Licheri, V., Adermark, L., & Jerlhag, E. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.04.008 · Cited by 16
Shi, X., Guan, K., Peng, X., Xu, B., Zhou, X.-Y., Wang, S., Xu, S., Zheng, M., Huang, J. Y., Wan, X., et al. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.12.029 · Cited by 16
Self-citationPark, S., King, S., MacDonald, D., Wilson, A., MacKay, H., Woodside, B. C., & Abizaid, A. B. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01350-6 · Cited by 16
Self-citationFeeding signals and drugs meet in the midbrain
Simerly, R. B. (2006) · Nature Medicine · doi:10.1038/nm1106-1244 · Cited by 16
Michopoulos, V., Loucks, T. L., Berga, S. L., Rivier, J., & Wilson, M. E. (2010) · Endocrine · doi:10.1007/s12020-010-9378-5 · Cited by 16
Subramaniam, M., Picco, L., He, V. Y., Vaingankar, J. A., Abdin, E., Verma, S. K., Rekhi, G., Yap, M., Lee, J., & Chong, S. A. (2012) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2012.10.009 · Cited by 16
“Several studies have addressed the role of ghrelin in brain reward systems [47,48] and an imbalance in the reward systems may cause addictive behaviors such as binge eating and alcoholism.”
BackgroundRoss, R., Mandelblat-Cerf, Y., & Verstegen, A. M. J. (2016) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000111 · Cited by 15
“Microinjection of ghrelin in the VTA of rats drives food intake—which is thought to be the basis of reward-driven eating behavior.(75,77) In fact, it was shown re-”
BackgroundPan, Y., Chau, L., Liu, S., Avshalumov, M. V., Rice, M. E., & Carr, K. D. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.08.065 · Cited by 17
“, 1993), as well as feeding-related peptides, including ghrelin (Abizaid et al., 2006) and orexin (Malherbe et al.”
BackgroundAn interoceptive model of energy allostasis linking metabolic and mental health
Mehrhof, S. Z., Fleming, H. A., & Nord, C. L. (2025) · Science Advances · doi:10.1126/sciadv.ady4356 · Cited by 22
“In rodents, VTA-administered ghrelin increases the firing rate of dopaminergic neurons and boosts both tonic and (food and drug) evoked striatal dopamine ( 85 , 86 ), as well as motivation to work for food rewards ( 85 , 87 ).”
Gray areas: Neuropeptide circuits linking the Edinger-Westphal and Dorsal Raphe nuclei in addiction
Pomrenze, M. B., Walker, L. C., & Giardino, W. J. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108769 · Cited by 16
Food reinforcement architecture: A framework for impulsive and compulsive overeating and food abuse
Burger, K. S. (2023) · Obesity · doi:10.1002/oby.23792 · Cited by 15
“GLP-1 receptors are located in the NAcc and VTA where they modulate the reward-related brain response to food [49–51].”
BackgroundSynaptic Plasticity of Feeding Circuits: Hormones and Hysteresis
Dietrich, M. O., & Horváth, T. L. (2011) · Cell · doi:10.1016/j.cell.2011.08.031 · Cited by 15
“Administration of ghrelin mimicked the effect of food deprivation on mEPSCs in in vitro experiments, consistent with ghrelin’s previously identified action on midbrain dopamine neurons (Abizaid et al., 2006).”
Result
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
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