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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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Foldi, C. J., Milton, L. K., & Oldfield, B. J. (2017) · Journal of Neuroendocrinology · doi:10.1111/jne.12479 · Cited by 40
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“More specifically, injection of ghrelin into reward areas has been shown to increase dopamine release in rodents, as well as increase subsequent dietary intake (Abizaid et al., 2006).”
Ghrelin mediated neuroprotection - A possible therapy for Parkinson's disease?
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“Additionally, circulating pancreatic and gut hormones such as insulin [47], PYY [13] and ghrelin [2] have been shown to directly modulate the activity of midbrain dopamine neurons.”
BackgroundThe Ghrelin Receptors (GHS-R1a and GHS-R1b)
Albarran-Zeckler, R. G., & Smith, R. G. (2013) · Endocrine development · doi:10.1159/000346042 · Cited by 39
Galanin – 25 years with a multitalented neuropeptide
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Self-citationBasic Aspects of Ghrelin Action
Pazos, Y., Casanueva, F. F., & Camiña, J. P. (2007) · Vitamins and hormones · doi:10.1016/s0083-6729(06)77005-4 · Cited by 39
Ghrelin receptor signaling in health and disease: a biased view
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Leptin in Early Life: A Key Factor for the Development of the Adult Metabolic Profile
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Implications from addiction research towards the understanding and treatment of obesity
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“Ghrelin receptors are located in dopaminergic neurons within the ventral tegmentum of the midbrain and stimulate the firing rate of neurons projecting to the NAC (Abizaid et al. 2006).”
BackgroundKing, S. J., Rodrigues, T., Watts, A. J., Murray, E. S., Wilson, A., & Abizaid, A. B. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.01.004 · Cited by 38
Self-citationSmall Molecule Ghrelin Receptor Inverse Agonists and Antagonists
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“It has been demonstrated that leptin, ghrelin and insulin, in addition to their homeostatic action in the hypothalamus, also target CNS circuit related to reward and motivation (Abizaid et al., 2006; Figlewicz et al., 2008; Hommel et al., 2006), which indicates that there is significant crosstalk between metabolic hor…”
Stevenson, J. R., Francomacaro, L. M., Bohidar, A. E., Young, K., Pesarchick, B. F., Buirkle, J. M., McMahon, E. K., & O'Bryan, C. M. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.12.017 · Cited by 37
Exercise for Weight Loss: Further Evaluating Energy Compensation with Exercise
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An Overview of Appetite-Regulatory Peptides in Addiction Processes; From Bench to Bed Side
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“), induces the dopaminergic reward pathway and dopamine release in NAc in rodents (Abizaid et al., 2006; Jerlhag, 2008; Quarta et al., 2009; Jerlhag et al., 2011a; Edvardsson et al., 2021).”
BackgroundPfluger, P. T., Castañeda, T. R., Heppner, K. M., Strassburg, S., Kruthaupt, T., Chaudhary, N., Halem, H. A., Culler, M. D., Datta, R., Burget, L., et al. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.04.025 · Cited by 37
“For instance, both NPY and various members of the NPY receptor family, as well as the ghrelin receptor GHSR, have been shown to be expressed in the midbrain ventral tegmental area (VTA), an area well known for its role in arousal, addiction, and the food reward system [46].”
BackgroundSelf-citationSystemic ghrelin and reward: Effect of cholinergic blockade
Disse, E., Bussier, A.-L., Deblon, N., Pfluger, P. T., Tschöp, M. H., Laville, M., & Rohner‐Jeanrenaud, F. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2010.12.006 · Cited by 38
“As a whole and on the basis of this, as well as other studies, it can be postulated that ghrelin could be involved in several kinds of rewards, being a common denominator in modulating reward [25].”
Self-citationImpaired wake‐promoting mechanisms in ghrelin receptor‐deficient mice
Esposito, M., Pellinen, J., Kapás, L., & Szentirmai, É. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07946.x · Cited by 35
“…(Guan et al., 1997; Mitchell et al., 2001; Zigman et al., 2006) and also found in extrahypothalamic brain regions, including the hippo- campus and nodes of the mesolimbic reward system, such as the ventral tegmental area (VTA) and nucleus accumbens (Abizaid et al., 2006; Skibicka et al., 2011).”
BackgroundInfluentialNeural correlates of plasma acylated ghrelin level in individuals with major depressive disorder
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“A cellular mechanism for the action of ghrelin was explained as that ghrelin stimulated VTA dopamine neurons via an increase in glutamate release [50].”
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“For example, ghrelin, an orexigenic hormone (87) that influences central dopamine (88) and serotonin (89), is increased in rodent plasma before scheduled meal times and changes in serum ghrelin concentrations have been correlated with higher or lower counts of certain fecal bacterial taxa (90).”
BackgroundBariatric Surgery and the Central Nervous System
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“Preclinical studies have shown ghrelin to effect signaling in the mesolimbic system [49–51].”
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Ghrelin and anorexia nervosa: A psychosomatic perspective
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“For example, leptin and insulin can dampen hedonic responses to food though action on dopaminergic neurons in the mesolimbic pathway [10], while grehlin facilitates reward processing [11].”
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An Evolutionary Perspective on the Obesity Epidemic
Hochberg, Z. (2018) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2018.09.002 · Cited by 35
Méquinion, M., Foldi, C. J., & Andrews, Z. B. (2020) · Frontiers in Nutrition · doi:10.3389/fnut.2019.00190 · Cited by 34
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“Recent findings suggest a direct effect of leptin [22] and ghrein [2] on the ventral tegmental area (VTA), the primary cell body ontaining area for the mesolimbic dopaminergic (DA) neurons, system that is recognized for its role in reward-related behavors [50].”
Tufvesson‐Alm, M., Shevchouk, O. T., & Jerlhag, E. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.1092828 · Cited by 33
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“Neurons in the VTA and/or NAc, express receptors for leptin [44,45], insulin [44], glucagon-like peptide-1 (GLP-1) [46], ghrelin [47,48], and orexin [49].”
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“…on dopaminergic neurons in the mesolimbic pathway; and ghrelin, as typically considered a homeostatic appetite hormone, has been seen to facilitate hedonic reward processes (Saper et al., 2002, Abizaid2006, Lutter and Nestler, 2009, Sominsky and Spencer, 2014; Reichelt et al., 2015, Steinbekk2017).”
GHS-R1a Deficiency Alleviates Depression-Related Behaviors After Chronic Social Defeat Stress
Guo, L., Niu, M., Yang, J., Li, L., Liu, S., Sun, Y., Zhou, Z., & Zhou, Y. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00364 · Cited by 34
Bae‐Gartz, I., Janoschek, R., Breuer, S., Schmitz, L., Hoffmann, T., Ferrari, N., Branik, L., Oberthuer, A., Kloppe, C.-S., Appel, S., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00962 · Cited by 34
“whereas ghrelin was found to impact synapse formation in various extra-hypothalamic brain regions (Abizaid et al., 2006; Diano et al., 2006).”
BackgroundAssociations between ghrelin and leptin and neural food cue reactivity in a fasted and sated state
Wever, M. C. M., van Meer, F., Charbonnier, L., Crabtree, D. R., Buosi, W., Giannopoulou, A., Androutsos, O., Johnstone, A. M., Μanios, Y., Meek, C. L., et al. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118374 · Cited by 34
Orquestic regulation of neurotransmitters on reward-seeking behavior
Arias-Carrión, Ó., Caraza-Santiago, X., Salgado-Licona, S., Salama, M., Machado, S. E. D. C., Nardi, A. E., Menéndez‐González, M., & Murillo‐Rodríguez, E. (2014) · International Archives of Medicine · doi:10.1186/1755-7682-7-29 · Cited by 37
“GHS-R1A is expressed pre and post-synaptically in the VTA [136] as well as on cholinergic neurons in the LDTg [137].”
BackgroundNarrative review on potential role of gut microbiota in certain substance addiction
Qin, C., Hu, J., Wan, Y., Cai, M., Wang, Z., Peng, Z., Liao, Y., Li, D., Yao, P., Liu, L., et al. (2021) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110093 · Cited by 32
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“, 2005) and ghrelin rapidly lowers the threshold of excitability in the VTA (Abizaid et al., 2006).”
BackgroundMethodSelf-citationJiang, J., Liu, H., Huang, Z., Cui, Y., Zhang, X., Zhang, X., Cui, Y., & Xin, W. (2016) · Addiction Biology · doi:10.1111/adb.12468 · Cited by 33
“performed by using 10 pA depolarizing current square pulses (Abizaid et al. 2006).”
MethodGupta, D., Patterson, A. M., Osborne-Lawrence, S. L., Bookout, A. L., Varshney, S., Shankar, K., Singh, O., Metzger, N. P., Richard, C. P., Wyler, S. C., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101258 · Cited by 32
“GHSR antagonist microinjection into the ventral tegmental area in the midbrain blocks the orexigenic effect of peripherally administered ghrelin [60].”
BackgroundThe controversial role of the vagus nerve in mediating ghrelin's actions: gut feelings and beyond
Perelló, M., Cornejo, M. P., Francesco, P. N. D., Fernández, G., Gautron, L., & Valdivia, L. S. (2022) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2022.03.003 · Cited by 32
Transcriptomics reveals amygdala neuron regulation by fasting and ghrelin thereby promoting feeding
Peters, C., He, S., Fermani, F., Lim, H., Ding, W., Mayer, C., & Klein, R. (2023) · Science Advances · doi:10.1126/sciadv.adf6521 · Cited by 29
“…(GHSR) (Howick et al., 2017), and through opioid and dopamine receptors, favoring food consumption by enhancing the hedonic and incentive responses to food-related cues (Abizaid et al., 2006; Engel et al., 2015; Kawahara et al., 2013; Kern et al., 2015; Skibicka et al., 2012; Yanagi et al., 2018).”
BackgroundDorsal striatum dopamine oscillations: Setting the pace of food anticipatory activity
de Lartigue, G., & McDougle, M. J. (2018) · Acta Physiologica · doi:10.1111/apha.13152 · Cited by 33
“However, ghrelin has been implicated in activating a mesolimbic dopaminergic pathway to promote feeding.(145) It has been suggested that mesolimbic circuit activation would prevent inhibition of downstream nigrostriatal circuits required for feeding,(56) and therefore, ghrelin may at least indirectly impact nigrostria…”
BackgroundEDITORIAL: Ghrelin: a link between energy homeostasis and drug abuse?
Cummings, D. E., Naleid, A. M., & Lattemann, D. F. (2007) · Addiction Biology · doi:10.1111/j.1369-1600.2007.00053.x · Cited by 31
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Neurobiology of Consummatory Behavior: Mechanisms Underlying Overeating and Drug Use
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“2007) as well as the VTA, dorsal raphe nucleus and even the hippocampus (Abizaid et al. 2006; Carlini et al. 2004).”
BackgroundSuchankova, P., Nilsson, S., von der Pahlen, B., Santtila, P. O., Sandnabba, K. N., Johansson, A., Jern, P., Engel, J. A., & Jerlhag, E. (2015) · Addiction Biology · doi:10.1111/adb.12277 · Cited by 31
“Firstly, Ghsr are expressed in nodes of this link including thenucleusaccumbens(NAc)(Landgren et al .2011b),on dopaminergic neurons in the ventral tegmental area (VTA) (Abizaid et al .”
Impact of food restriction and cocaine on locomotion in ghrelin- and ghrelin-receptor knockout mice
Clifford, S., Albarran-Zeckler, R. G., Buckman, S., Thompson, J., Hart, N., Wellman, P. J., & Smith, R. G. (2010) · Addiction Biology · doi:10.1111/j.1369-1600.2010.00253.x · Cited by 31
“Systemic ghrelin is passively transported across the blood–brain barrier (Banks et al. 2002; Diano et al. 2006; Banks, Burney & Robinson 2008) and ghrelin receptors have been located on brain dopamine neurons (Guan et al. 1997; Naleid et al. 2005; Abizaid et al. 2006; Diano et al. 2006).”
BackgroundPruimboom, L., Raison, C. L., & Muskiet, F. A. J. (2015) · Behavioural Neurology · doi:10.1155/2015/569869 · Cited by 32
Ghrelin: New Molecular Pathways Modulating Appetite and Adiposity
Nogueiras, R., Williams, L. M., & Diéguez, C. (2010) · Obesity Facts · doi:10.1159/000321265 · Cited by 30
Hägglund, M. G. A., Roshanbin, S., Löfqvist, E., Hellsten, S. V., Nilsson, V. C., Todkar, A., Zhu, Y., Stephansson, O., Drgonová, J., Uhl, G. R., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058651 · Cited by 32
“are areas known to be part of the regulation of food intake [32,33].”
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“Importantly, pharmacological activation of GHSR in VTA DA neurons stimulates neuronal firing, promotes food-seeking behavior, and controls alcohol intake (12,13,30).”
BackgroundDeschaine, S. L., Farokhnia, M., Gregory‐Flores, A., Zallar, L. J., You, Z., Sun, H., Harvey, D. M., Marchette, R. C. N., Tunstall, B. J., Mani, B. K., et al. (2021) · Addiction Biology · doi:10.1111/adb.13033 · Cited by 30
Regulation of food intake: The gastric X/A-like endocrine cell in the spotlight
Stengel, A., & Taché, Y. (2009) · Current Gastroenterology Reports · doi:10.1007/s11894-009-0069-4 · Cited by 30
“Behavioral studies showed that a single intrategmental infusion of ghrelin significantly increases food intake during the first 2 hours after treatment [46].”
BackgroundRatner, C., Madsen, A. N., Kristensen, L. V., Skov, L. J., Pedersen, K. S., Mortensen, O. H., Knudsen, G. M., Raun, K., & Holst, B. (2015) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00219.2014 · Cited by 31
“The ghrelin dose was chosen based on previous publications (1, 5) and further optimized in our laboratory; in lean rats, this dose increases the active ghrelin concentration about fivefold from 903 82 pg/ml to 4,393 162 pg/ml in plasma after 40 min (Ratner C, Skov LJ, Madsen AN, and Holst B; unpublished observations).”
MethodThe antagonism of ghrelin alters the appetitive response to learned cues associated with food.
Dailey, M. J., Moran, T., Holland, P., & Johnson, A. W. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.01.040 · Cited by 35
Sun, X., Veldhuizen, M. G., Babbs, A. E., Sinha, R., & Small, D. M. (2016) · Chemical Senses · doi:10.1093/chemse/bjv081 · Cited by 33
Anorexia in rats caused by a valine-deficient diet is not ameliorated by systemic ghrelin treatment
Goto, S., Nagao, K., Bannai, M., Takahashi, M., Nakahara, K., Kangawa, K., & MURAKAMI, N. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.12.013 · Cited by 29
Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning
Mills, F., Globa, A. K., Liu, S., Cowan, C. M., Mobasser, M., Phillips, A. G., Borgland, S. L., & Bamji, S. X. (2017) · Nature Neuroscience · doi:10.1038/nn.4503 · Cited by 30
Plasticity of calcium-permeable AMPA glutamate receptors in Pro-opiomelanocortin neurons
Suyama, S., Ralevski, A., Liu, Z. W., Dietrich, M. O., Yada, T., Simonds, S. E., Cowley, M. A., Gao, X., Diano, S., & Horváth, T. L. (2017) · eLife · doi:10.7554/elife.25755 · Cited by 27
“Under food restriction, the NPY/AgRP neurons are activated and synaptic plasticity occurs in these cells (Abizaid et al., 2006; Andrews et al., 2008; Dietrich et al., 2010; Dietrich and Horvath, 2011; Granger et al., 2011; Liu and Zukin, 2007; Liu et al., 2012), whereas POMC neurons are inhibited and the levels of POM…”
BackgroundSelf-citationŠustková-Fišerová, M., Charalambous, C., Havlickova, T., Lapka, M., Jerabek, P., Puskina, N., & Syslová, K. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112486 · Cited by 29
“The used coordinates to target the VTA district linked with ghrelin-involving food/drug motivation are chosen following literature [7,12].”
MethodHavlickova, T., Charalambous, C., Lapka, M., Puskina, N., Jeřábek, P., & Sustkova-Fiserova, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19102925 · Cited by 30
Oxytocin as an Anti-obesity Treatment
Niu, J., Tong, J., & Blevins, J. E. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.743546 · Cited by 30
Seasonal changes in the interactions among leptin, ghrelin, and orexin in sheep1
Kirsz, K., Szczęsna, M., Molik, E., Misztal, T., Wójtowicz, A. K., & Zieba, D. A. (2012) · Journal of Animal Science · doi:10.2527/jas.2011-4463 · Cited by 28
“…among ghrelin and clock peptides sheds new light on the mechanism by which the energy economy of the body is regulated in the context of diurnal changes and demonstrates the participation of peripherally synthesized factors, such as ghrelin and leptin, in these processes (Abizaid et al., 2006).”
BackgroundCahill, S. P., Hatchard, T., Abizaid, A. B., & Holahan, M. R. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.02.004 · Cited by 29
Self-citationPhysiological role of ghrelin as revealed by the ghrelin and GOAT knockout mice
Kang, K., Zmuda, E. J., & Sleeman, M. W. (2011) · Peptides · doi:10.1016/j.peptides.2011.04.028 · Cited by 29
Self-citationAddolorato, G., Leggio, L., Hillemacher, T., Kraus, T., Jerlhag, E., & Bleich, S. (2009) · Drug and Alcohol Review · doi:10.1111/j.1465-3362.2008.00023.x · Cited by 29
“Considering that the ghrelin levels in the hypothalamus are higher in patients with obesity than in lean subjects [26] and that compulsive overeating has been associated with aberrations in the central DA system [27] and that ghrelin activates the mesolimbic DA systems [20,21,23], it might be implied that high ghrelin…”
BackgroundRole of mesolimbic ghrelin in the acquisition of cocaine reward
Dunn, D. P., Bastacky, J. M. R., Gray, C. C., Abtahi, S., & Currie, P. J. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134367 · Cited by 29
Increased Ghrelin Levels and Unchanged Adipocytokine Levels in Major Depressive Disorder
Tunçel, Ö. K., Akbaş, S., & Bilgici, B. (2016) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2015.0149 · Cited by 29
Decoding the influence of central LEAP2 on food intake and its effect on accumbal dopamine release
Tufvesson‐Alm, M., Zhang, Q., Aranäs, C., Sköldheden, S. B., Edvardsson, C. E., & Jerlhag, E. (2024) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2024.102615 · Cited by 28
“This raises the possibility that LEAP2 has a function within the brain to influence food intake through central reward processes via the GHSR.”
InfluentialNavarro, G., Rea, W. P., Quiroz, C., Moreno, E., Gomez, D. M., Wenthur, C. J., Casadó, V., Leggio, L., Hearing, M. C., & Ferré, S. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.1151-21.2021 · Cited by 28
“Indeed, past work has shown that ghrelin-mediated increases in the firing frequency of putative VTA dopaminergic neurons are inhibited by blockade of AMPA- and NMDA-type glutamate receptors and align with elevations in the frequency of miniature excitatory postsynaptic currents—a phenomenon often equated with increase…”
BackgroundMethodInfluentialGrowth hormone biases amygdala network activation after fear learning
Gisabella, B., Farah, S., Peng, X., Burgos-Robles, A., Lim, S. H., & Goosens, K. A. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.203 · Cited by 28
D’Cunha, T. M., Chisholm, A., Hryhorczuk, C., Fulton, S., & Shalev, U. (2019) · Psychopharmacology · doi:10.1007/s00213-019-05415-9 · Cited by 27
Lee, J., Raycraft, L. M., & Johnson, A. W. (2020) · Physiology & Behavior · doi:10.1016/j.physbeh.2020.113234 · Cited by 30
“Additionally, the DA release resulting directly from ghrelin [204] and/or ORX [47, 132] might also serve to dampen MCH activity [205].”
BackgroundSavage, S. W., Zald, D. H., Cowan, R. L., Volkow, N. D., Marks-Shulman, P. A., Kessler, R. M., Abumrad, N. N., & Dunn, J. P. (2014) · Obesity · doi:10.1002/oby.20690 · Cited by 27
“Acyl ghrelin enhances DA cell firing properties (27), and a reduction in autoreceptor control will similarly enhance DA release when stimulated (8).”
Impact of Antidepressants on Weight Gain: Underlying Mechanisms and Mitigation Strategies
Mouawad, M., Nabipur, L., & Agrawal, D. K. (2025) · Archives of Clinical and Biomedical Research · doi:10.26502/acbr.50170450 · Cited by 27
“In contrast, ghrelin, which is secreted from the stomach and has receptors in the mesolimbic circuits, has the opposite effect—it enhances dopamine release and activity in the VTA, promoting food intake [88].”
Nutritional Controls of Food Reward
Fernandes, M. F., Sharma, S., Hryhorczuk, C., Auguste, S., & Fulton, S. (2013) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2013.04.004 · Cited by 27
Gastroenteric hormone responses to hedonic eating in healthy humans
Monteleone, P., Scognamiglio, P., Monteleone, A. M., Perillo, D., Canestrelli, B., & Maj, M. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.12.009 · Cited by 27
Shan, X., & Yeo, G. S. H. (2011) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-011-9171-7 · Cited by 28
“Such an effect is absent in Ghsr knockout mice [62].”
BackgroundInfluentialGenetic Variation of the Ghrelin Signalling System in Individuals with Amphetamine Dependence
Suchankova, P., Jerlhag, E., Jayaram‐Lindström, N., Nilsson, S., Torén, K., Rosengren, A., Engel, J. A., & Franck, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061242 · Cited by 26
“Centrally or peripherally administered ghrelin has also been shown to activate the reward systems, specifically the cholinergic-dopaminergic reward link [14–18], and may thereby increase the incentive value of motivated behaviours such as food seeking.”
Association between plasma ghrelin and motilin levels during MMC cycle in conscious dogs
Zietlow, A. M., Nakajima, H., Taniguchi, H., Ludwig, K., & Takahashi, T. (2010) · Regulatory Peptides · doi:10.1016/j.regpep.2010.05.006 · Cited by 26
Cerit, H., Christensen, K. A., Moondra, P., Klibanski, A., Goldstein, J. M., & Holsen, L. M. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.07.088 · Cited by 25
“Within the VTA, ghrelin receptors are expressed on dopaminergic neurons (Jiang et al., 2006; Kern et al., 2012; Schellekens et al., 2013).”
BackgroundInfluentialKokkinos, A. D., Tsilingiris, D., le Roux, C. W., Rubino, F., & Mantzoros, C. S. (2019) · Metabolism · doi:10.1016/j.metabol.2019.153960 · Cited by 28
Blanco-Gandía, M. C., Miñarro, J., & Rodríguez‐Arias, M. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612826666200213123608 · Cited by 28
Ribeiro, L. F., Catarino, T., de Carvalho, M. L., Cortes, L., Santos, S. D., Opazo, P., Ribeiro, L. R., Oliveiros, B., Choquet, D., Esteban, J. A., et al. (2021) · Science Signaling · doi:10.1126/scisignal.abb1953 · Cited by 25
“For example, it is well established that ghrelin improves learning and memory (9, 10), facilitates reward through its action on the mesolimbic dopamine system (11), modulates anxiety-like (9) and depressive-like (12) behaviors, and enhances long-term fear memory (13).”
BackgroundGastelum, C., Perez, L., Hernandez, J., Le, N., Vahrson, I., Sayers, S., & Wagner, E. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052728 · Cited by 27
“Furthermore, ghrelin binding to and activating ghrelin receptors expressed on A 10 dopamine neurons has been shown to elevate the frequency of action potentials in these neurons, as well as induce increased dopamine turnover in the NAc, promoting appetite [97].”
Gut-brain peptides in corticostriatal-limbic circuitry and alcohol use disorders
Vadnie, C. A., Park, J. H., Gawad, N. A., Ho, A. M., Hinton, D. J., & Choi, D. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00288 · Cited by 26
“GHS-R1a is expressed presynaptically and postsynaptically in the VTA (Abizaid et al., 2006) as well as on cholinergic neurons in the laterodorsal tegmental area (LDTg) (Dickson et al., 2010).”
BackgroundInfluential
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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