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The Melanocortinergic Pathway Is Rapidly Recruited by Emotional Stress and Contributes to Stress-Induced Anorexia and Anxiety-Like Behavior
Open accessAbstract
Neurons producing melanocortin receptor agonist, alpha-MSH derived from proopiomelanocortin, and antagonist, agouti-related protein, are known to be sensitive to metabolic stress such as food deprivation and glucoprivation. However, how these neurons respond to emotional/psychological stress remained to be elucidated. We report here that acute emotional stressors, i.e. restraint and forced swim, evoked mRNA expression of c-fos, a neuronal activation marker, in a high percentage of proopiomelanocortin neurons (up to 53% for restraint stress and 62% for forced swim), with marked variations along the rostro-caudal axis of the arcuate nucleus. In contrast, only a small population of agouti-related protein neurons in this brain region was activated. These neuronal activation patterns were correlated with behavioral reactions. Both stressors suppressed feeding and induced anxiety-like behavior in the elevated plus-maze test, as reflected by a reduction in the percentage of entries and time spent in the open arms. Central pretreatment with SHU9119, a melanocortin receptor antagonist, dose dependently attenuated the anorectic and anxiogenic effects elicited by acute restraint or forced swim. These results indicate that the melancortinergic pathway can be rapidly recruited by acute emotional stress, and that activation of melanocortin signaling is involved in mediating stress-induced anorexia and anxiety.
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“We and others have previously shown that neurons in the arcuate nucleus (ARC) of the hypothalamus are activated by emotional stimuli [16, 17].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [16]
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“We have previously demonstrated that AgRP neurons can respond rapidly to acute emotional stress [16].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [16]
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Cites
The Emotional Brain: The Mysterious Underpinnings of Emotional Life
LeDoux, J. E. (2004) · Medical Entomology and Zoology · Cited by 4,212
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
Cowley, M. A., Smart, J. L., Rubinstein, M., Cerdán, M. G., Diano, S., Horvath, T. L., Cone, R. D., & Low, M. J. (2001) · Nature · doi:10.1038/35078085 · Cited by 2,356
Neurocircuitry of stress: central control of the hypothalamo–pituitary–adrenocortical axis
Herman, J. P., & Cullinan, W. E. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)10069-2 · Cited by 2,270
Expression of c- fos Protein in Brain: Metabolic Mapping at the Cellular Level
Sagar, S. M., Sharp, F. R., & Curran, T. (1988) · Science · doi:10.1126/science.3131879 · Cited by 1,925
Role of melanocortinergic neurons in feeding and the agouti obesity syndrome
Fan, W., Boston, B. A., Kesterson, R. A., Hruby, V. J., & Cone, R. D. (1997) · Nature · doi:10.1038/385165a0 · Cited by 1,924
The use of c-fos as a metabolic marker in neuronal pathway tracing
Dragunow, M., & Faull, R. (1989) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(89)90150-7 · Cited by 1,416
Divergence of Melanocortin Pathways in the Control of Food Intake and Energy Expenditure
Balthasar, N., Dalgaard, L. T., Lee, C. E., Yu, J. H., Funahashi, H., Williams, T. B., Ferreira, M. A. R., Tang, V., McGovern, R. A., Kenny, C. D., et al. (2005) · Cell · doi:10.1016/j.cell.2005.08.035 · Cited by 1,107
Bullitt, E. (1990) · Journal of Comparative Neurology · doi:10.1002/cne.902960402 · Cited by 1,059
Pattern and time course of immediate early gene expression in rat brain following acute stress
Cullinan, W. E., Herman, J. P., Battaglia, D. F., Akil, H., & Watson, S. J. (1995) · Neuroscience · doi:10.1016/0306-4522(94)00355-9 · Cited by 1,056
Anxiety, defence and the elevated plus-maze.
Rodgers, R., & Dalvi, A. (1997) · Neuroscience and Biobehavioral Reviews · doi:10.1016/s0149-7634(96)00058-9 · Cited by 1,028
Leptin Differentially Regulates NPY and POMC Neurons Projecting to the Lateral Hypothalamic Area
Elias, C. F., Aschkenasi, C., Lee, C., Kelly, J., Ahima, R. S., Bjorbæk, C., Flier, J. S., Saper, C. B., & Elmquist, J. K. (1999) · Neuron · doi:10.1016/s0896-6273(01)80035-0 · Cited by 924
Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat
Kishi, T., Aschkenasi, C. J., Lee, C. E., Mountjoy, K. G., Saper, C. B., & Elmquist, J. K. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10454 · Cited by 581
Rossi, M., Kim, M. S., Morgan, D. G. A., Small, C. J., Edwards, C. M. B., Sunter, D., Abusnana, S., Goldstone, A. P., Russell, S. H., Stanley, S. A., et al. (1998) · Endocrinology · doi:10.1210/endo.139.10.6332 · Cited by 576
Response of melanocortin–4 receptor–deficient mice to anorectic and orexigenic peptides
Marsh, D. J., Hollopeter, G., Huszar, D., Laufer, R., Yagaloff, K. A., Fisher, S. L., Burn, P., & Palmiter, R. D. (1999) · Nature Genetics · doi:10.1038/5070 · Cited by 547
Pynoos, R. S., Steinberg, A. M., & Piacentini, J. C. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00262-0 · Cited by 534
Dayas, C. V., Buller, K. M., Crane, J. W., Xu, Y., & Day, T. A. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01733.x · Cited by 514
Bagnol, D., Lu, X.-Y., Kaelin, C. B., Day, H. E. W., Ollmann, M., Gantz, I., Akil, H., Barsh, G. S., & Watson, S. J. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-18-j0004.1999 · Cited by 425 · cited 5×
“Anatomical studies demonstrate that -MSH and AgRP neurons innervate a variety of brain regions that have been well characterized in stress reactions (4).”
BackgroundMethodInfluentialSelf-citationThe contribution of the amygdala to normal and abnormal emotional states
Aggleton, J. P. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90110-8 · Cited by 423
Mizuno, T. M., & Mobbs, C. V. (1999) · Endocrinology · doi:10.1210/endo.140.2.6491 · Cited by 406
Jacobowitz, D. M., & O’Donohue, T. L. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.12.6300 · Cited by 354
Circuits and mechanisms governing hypothalamic responses to stress: a tale of two paradigms
Sawchenko, P. E., Li, H.-Y., & Ericsson, A. B. (2000) · Progress in brain research · doi:10.1016/s0079-6123(08)62131-7 · Cited by 353
Takahashi, K. A., & Cone, R. D. (2005) · Endocrinology · doi:10.1210/en.2004-1397 · Cited by 308
Dayas, C. V., Buller, K. M., & Day, T. A. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00645.x · Cited by 303
Coppola, A., Liu, Z.-W., Andrews, Z. B., Paradis, E., Roy, M.-C., Friedman, J. M., Ricquier, D., Richard, D., Horvath, T. L., Gao, X.-B., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2006.12.002 · Cited by 295
Chan, R., Brown, E., Ericsson, A., Kovacs, K., & Sawchenko, P. (1993) · The Journal of Neuroscience · doi:10.1523/jneurosci.13-12-05126.1993 · Cited by 289
Grill, H. J., Ginsberg, A. B., Seeley, R. J., & Kaplan, J. M. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-23-10128.1998 · Cited by 277
Lu, X., Barsh, G. S., Akil, H., & Watson, S. J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-21-07863.2003 · Cited by 240
Self-citationO’Donohue, T. L., Miller, R. L., & Jacobowitz, D. M. (1979) · Brain Research · doi:10.1016/0006-8993(79)90873-4 · Cited by 228
Ebner, K., Rupniak, N. M. J., Saria, A., & Singewald, N. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400794101 · Cited by 225
Kim, M. S., Rossi, M., Abusnana, S., Sunter, D., Morgan, D. G., Small, C. J., Edwards, C. M., Heath, M., Stanley, S. A., Seal, L., et al. (2000) · Diabetes · doi:10.2337/diabetes.49.2.177 · Cited by 216
Behavioral effects of α-MSH and MCH after central administration in the female rat
González, M. I., Vaziri, S. M., & Wilson, C. A. (1996) · Peptides · doi:10.1016/0196-9781(95)02092-6 · Cited by 193
Thiele, T. E., van Dijk, G., Yagaloff, K. A., Fisher, S. L., Schwartz, M. W., Burn, P., & Seeley, R. J. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.274.1.r248 · Cited by 177
McMinn, J. E., Wilkinson, C. W., Havel, P. J., Woods, S. C., & Schwartz, M. W. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.279.2.r695 · Cited by 156
Induction and adaptation of Fos expression in the rat brain by two types of acute restraint stress
Mohammad, G., Chowdhury, I., Fujioka, T., & Nakamura, S. (2000) · Brain Research Bulletin · doi:10.1016/s0361-9230(00)00231-8 · Cited by 153
THE CRITICAL ROLE OF THE MELANOCORTIN SYSTEM IN THE CONTROL OF ENERGY BALANCE
Seeley, R. J., Drazen, D. L., & Clegg, D. J. (2004) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.24.012003.132428 · Cited by 145
“The role of melanocortins in body weight regulation: opportunities for the treatment of obesity”
MacNeil, D. J., Howard, A. D., Guan, X.-M., Fong, T. M., Nargund, R. P., Bednarek, M. A., Goulet, M. T., Weinberg, D. H., Strack, A. M., Marsh, D. J., et al. (2002) · European Journal of Pharmacology · doi:10.1016/s0014-2999(02)01989-1 · Cited by 137
Role of melanocortins in the central control of feeding
Vergoni, A. V., & Bertolini, A. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00538-0 · Cited by 125
Sergeyev, V., Broberger, C., Gorbatyuk, O. S., & Hökfelt, T. (2000) · Neuroreport · doi:10.1097/00001756-200001170-00023 · Cited by 119
Neurobiology of generalized anxiety disorder.
Jetty, P. V., Charney, D., & Goddard, A. W. (2001) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(05)70207-0 · Cited by 116
Duxon, M. S., Kennett, G. A., Lightowler, S., Blackburn, T. P., & Fone, K. C. F. (1997) · Neuropharmacology · doi:10.1016/s0028-3908(97)00042-7 · Cited by 103
Adan, R. A. H., Szklarczyk, A., Oosterom, J., Brakkee, J. H., Nijenhuis, W. A. J., Schaaper, W. M. M., Meloen, R. H., & Gispen, W. H. (1999) · European Journal of Pharmacology · doi:10.1016/s0014-2999(99)00465-3 · Cited by 103
Fraley, G. S., & Ritter, S. (2002) · Endocrinology · doi:10.1210/en.2002-220659 · Cited by 92
Diurnal Rhythm of Agouti-Related Protein and Its Relation to Corticosterone and Food Intake
Lu, X., Shieh, K.-R., Kabbaj, M., Barsh, G. S., Akil, H., & Watson, S. J. (2002) · Endocrinology · doi:10.1210/en.2002-220150 · Cited by 87
Self-citationInvolvement of the melanocortin MC4 receptor in stress-related behavior in rodents
Chaki, S., Ogawa, S., Toda, Y., Funakoshi, T., & Okuyama, S. (2003) · European Journal of Pharmacology · doi:10.1016/s0014-2999(03)02033-8 · Cited by 86
Morinobu, S., Nibuya, M., & Duman, R. S. (1995) · Neuropsychopharmacology · doi:10.1016/0893-133x(94)00067-a · Cited by 77
Overview and Clinical Presentation of Generalized Anxiety Disorder
Rickels, K., & Rynn, M. A. (2001) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(05)70203-3 · Cited by 66
Chowen, J. A., Clifton, D. K., & Steiner, R. A. (1989) · Endocrinology · doi:10.1210/endo-124-6-2875 · Cited by 65
The role of melanocortins in body weight regulation: opportunities for the treatment of obesity
MacNeil, D. J., Howard, A. D., Guan, X.-M., Fong, T. M., Nargund, R. P., Bednarek, M. A., Goulet, M. T., Weinberg, D. H., Strack, A. M., Marsh, D. J., et al. (2002) · European Journal of Pharmacology · doi:10.1016/s0014-2999(02)01425-5 · Cited by 64
Forestiero, D., Manfrim, C. M., Guimarães, F. S., & de Oliveira, R. M. W. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0270-6 · Cited by 62
AgRP in energy balance: Will the real AgRP please stand up?
Flier, J. S. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.003 · Cited by 60
WIEMANN, J. N., Clifton, D. K., & Steiner, R. A. (1989) · Endocrinology · doi:10.1210/endo-124-4-1760 · Cited by 59
Minami, S., Kamegai, J., Sugihara, H., Suzuki, N., Higuchi, H., & Wakabayashi, I. (1995) · Molecular Brain Research · doi:10.1016/0169-328x(95)00151-h · Cited by 57
GABAergic agents prevent alpha-melanocyte stimulating hormone induced anxiety and anorexia in rats
Rao, T. L., Kokare, D. M., Sarkar, S., Khisti, R. T., Chopde, C. T., & Subhedar, N. K. (2003) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2003.08.016 · Cited by 55
Animal Models of Human Eating Disordersa
Smith, G. P. (1989) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1989.tb53233.x · Cited by 53
Role of Central Melanocortin Signaling in Eating Disorders
Lu, X., PhD, & Rush, A. J. (2025) · Psychopharmacology Bulletin · doi:10.64719/pb.4239 · Cited by 43
Self-citationWagner, C. G., McMahon, C. D., Marks, D. L., Daniel, J. A., Steele, B., & Sartin, J. L. (2004) · Neuroendocrinology · doi:10.1159/000082735 · Cited by 39
Holden, R. J., & Pakula, I. S. (1999) · Medical Hypotheses · doi:10.1054/mehy.1997.0641 · Cited by 35
Alpha MSH-induced excessive grooming behavior involves a GABAergic mechanism
de Barioglio, S. R., Lezcano, N. E., & Celis, M. E. (1991) · Peptides · doi:10.1016/0196-9781(91)90189-v · Cited by 31
Social stress in anorexia nervosa: a review of immuno-endocrine relationships
Brambilla, F. (2001) · Physiology & Behavior · doi:10.1016/s0031-9384(01)00457-7 · Cited by 29
Familial Psychiatric Illness and Posttraumatic Stress Disorder
Dierker, L., & Merikangas, K. R. (2001) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v62n0909 · Cited by 18
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Nixon, A. E., Mazzola, J. J., Bauer, J. A., Krueger, J. R., & Spector, P. E. (2011) · Work & Stress · doi:10.1080/02678373.2011.569175 · Cited by 672
Anhedonia requires MC4R-mediated synaptic adaptations in nucleus accumbens
Lim, B. K., Huang, K. W., Grueter, B. A., Rothwell, P. E., & Malenka, R. C. (2012) · Nature · doi:10.1038/nature11160 · Cited by 368
The link between stress and feeding behaviour
Maniam, J., & Morris, M. J. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.04.017 · Cited by 273
Garza, J. C., Guo, M., Zhang, W., & Lu, X.-Y. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.161 · Cited by 209
Self-citationYosten, G. L. C., & Samson, W. K. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90867.2008 · Cited by 209
Metadata
- Authors
- Liu, J., Garza, J. C., Truong, H. V., Henschel, J., Zhang, W., & Lu, X.-Y.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2007-11
- Volume
- 148
- Issue
- 11
- Pages
- 5531-5540
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC3708592
- OpenAlex
- W1977763506
- Cited by
- 141
- References
- 60
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 2 · 2023: 8 · 2022: 10 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 7 · 2016: 8 · 2015: 7 · 2014: 7 · 2013: 7 · 2012: 9
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH076929, R01MH073844)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Keywords
- emotional stress, stress-induced anorexia, anxiety-like behavior, proopiomelanocortin neurons, agouti-related protein, arcuate nucleus, Fos expression, restraint stress, forced swim test, SHU9119, feeding inhibition
- MeSH terms
- Animals, Anorexia, Anxiety, Behavior, Animal, Corticosterone, Male, Neurons, Pro-Opiomelanocortin, Restraint, Physical, Stress, Psychological, Swimming, Signal Transduction, Genes, fos, Rats, Sprague-Dawley, Leptin, Gene Expression Profiling, Rats, Melanocortins, Agouti-Related Protein
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