Skip to main content

Advertisement

SpringerLink
Log in

The Role of Melanin-Concentrating Hormone in Energy Homeostasis and Mood Disorders

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

The melanin-concentrating hormone (MCH) is a cyclic peptide exerting its actions through two G-protein-coupled receptors, MCHR1 and MCHR2. MCH is implicated in the regulation of different physiological functions, including energy homeostasis and mood that is supported by the distribution of MCH and MCHR1 in the hypothalamus as well as corticolimbic structures. Genetic manipulation of MCH and MCHR1 results in a lean phenotype with increased resting energy expenditure as well as anxiolytic and antidepressant phenotypes. Similar observations have been demonstrated pharmacologically using different classes of selective MCHR1 antagonists. Here, we summarize the reported genetic and pharmacological evidence for the role played by the MCH system in the regulation of both energy homeostasis and mood disorders. We also comment on the utility of small-molecule MCHR1 antagonists for the treatment of obesity and affective disorders compared to existing therapies and provide a critical overview of the potential risks.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adamantidis, A., Thomas, E., Foidart, A., Tyhon, A., Coumans, B., Minet, A., et al. (2005). Disrupting the melanin-concentrating hormone receptor 1 in mice leads to cognitive deficits and alterations of NMDA receptor function. The European Journal of Neuroscience, 21, 2837–2844. doi:10.1111/j.1460-9568.2005.04100.x.

    Article  PubMed  Google Scholar 

  • Ahnaou, A., Drinkenburg, W. H. I. M., Bouwknecht, J. A., Alcazar, J., Steckler, T., & Dautzenberg, F. M. (2008). Blocking melanin-concentrating hormone MCH1 receptor affects rat sleep-wake architecture. European Journal of Pharmacology, 579, 177–188. doi:10.1016/j.ejphar.2007.10.017.

    Article  PubMed  CAS  Google Scholar 

  • Alon, T., & Friedman, J. M. (2006). Late-onset leanness in mice with targeted ablation of melanin concentrating hormone neurons. The Journal of Neuroscience, 26, 389–397. doi:10.1523/JNEUROSCI.1203-05.2006.

    Article  PubMed  CAS  Google Scholar 

  • An, S., Cutler, G., Zhao, J. J., Huang, S.-G., Tian, H., Li, W., et al. (2001). Identification and characterization of a melanin-concentrating hormone receptor. Proceedings of the National Academy of Sciences of the United States of America, 98, 7576–7581. doi:10.1073/pnas.131200698.

    Article  PubMed  CAS  Google Scholar 

  • Anand, B. K., & Brobeck, J. R. (1951). Localisation of a ‘feeding center’ in the hypothalamus of the rat. Proceedings of the Society for Experimental Biology and Medicine, 77, 323–324.

    PubMed  CAS  Google Scholar 

  • Antal Zimányi, I., & Poindexter, G. S. (2000). NPY-ergic agents for the treatment of obesity. Drug Development Research, 51, 94–111. doi:10.1002/1098-2299(200010)51:2<94::AID-DDR5>3.0.CO;2-Z.

    Article  Google Scholar 

  • Arriaga, F., Dugovic, C., & Wauquier, A. (1988). Effects of lithium on dopamine behavioural supersensitivity induced by rapid eye movement sleep deprivation. Neuropsychobiology, 20, 23–27. doi:10.1159/000118468.

    Article  PubMed  CAS  Google Scholar 

  • Astrand, A., Bohlooly-Y, M., Larsdotter, S., Mahlapuu, M., Andersen, H., Tornell, J., et al. (2004). Mice lacking melanin-concentrating hormone receptor 1 demonstrate increased heart rate associated with altered autonomic activity. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 287, R749–R758. doi:10.1152/ajpregu.00134.2004.

    PubMed  CAS  Google Scholar 

  • Basso, A. M., Bratcher, N. A., Gallagher, K. B., Cowart, M. D., Zhao, C., Sun, M., et al. (2006). Lack of efficacy of melanin-concentrating hormone-1 receptor antagonists in models of depression and anxiety. European Journal of Pharmacology, 540, 115–120. doi:10.1016/j.ejphar.2006.04.043.

    Article  PubMed  CAS  Google Scholar 

  • Bauer, M., Whybrow, P. C., Angst, J., Versiani, M., & MÃller, H.-J. (2002a). World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: Acute and continuation treatment of major depressive disorder. The World Journal of Biological Psychiatry, 3, 5–43. doi:10.3109/15622970209150599.

    Article  PubMed  Google Scholar 

  • Bauer, M., Whybrow, P. C., Angst, J., Versiani, M., & MÃller, H.-J. (2002b). World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 2: Maintenance treatment of major depressive disorder and treatment of chronic depressive disorders and subthreshold depressions. The World Journal of Biological Psychiatry, 3, 69–86. doi:10.3109/15622970209150605.

    Article  PubMed  Google Scholar 

  • Bednarek, M. A., Hreniuk, D. L., Tan, C., Palyha, O. C., MacNeil, D. J., Van der Ploeg, L. H., et al. (2002). Synthesis and biological evaluation in vitro of selective, high affinity peptide antagonists of human melanin-concentrating hormone action at human melanin-concentrating hormone receptor 1. Biochemistry, 41, 6383–6390. doi:10.1021/bi0200514.

    Article  PubMed  CAS  Google Scholar 

  • Bittencourt, J. C., Presse, F., Arias, C., Peto, C., Vaughan, J., Nahon, J. L., et al. (1992). The melanin-concentrating hormone system of the rat brain: An immuno- and hybridization histochemical characterization. The Journal of Comparative Neurology, 319, 218–245. doi:10.1002/cne.903190204.

    Article  PubMed  CAS  Google Scholar 

  • Bluet-Pajot, M. T., Presse, F., Voko, Z., Hoeger, C., Mounier, F., Epelbaum, J., et al. (1995). Neuropeptide-E-I antagonizes the action of melanin-concentrating hormone on stress-induced release of adrenocorticotropin in the rat. Journal of Neuroendocrinology, 7, 297–303. doi:10.1111/j.1365-2826.1995.tb00761.x.

    Article  PubMed  CAS  Google Scholar 

  • Bohlooly, Y. M., Mahlapuu, M., Andersen, H., Astrand, A., Hjorth, S., Svensson, L., et al. (2004). Osteoporosis in MCHR1-deficient mice. Biochemical and Biophysical Research Communications, 318, 964–969. doi:10.1016/j.bbrc.2004.04.122.

    Article  Google Scholar 

  • Borowsky, B., Durkin, M. M., Ogozalek, K., Marzabadi, M. R., DeLeon, J., Heurich, R., et al. (2002). Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist. Nature Medicine, 8, 825–830.

    PubMed  CAS  Google Scholar 

  • Bradley, R. L., Mansfield, J. P., Maratos-Flier, E., & Cheatham, B. (2002). Melanin-concentrating hormone activates signaling pathways in 3 T3–L1 adipocytes. American Journal of Physiology. Endocrinology and Metabolism, 283, E584–E592.

    PubMed  CAS  Google Scholar 

  • Carlini, V. P., Schioth, H. B., & de Barioglio, S. R. (2006). Melanin-concentrating hormone (MCH) reverts the behavioral effects induced by inescapable stress. Peptides, 27, 2300–2306. doi:10.1016/j.peptides.2006.03.009.

    Article  PubMed  CAS  Google Scholar 

  • Carr, K. D. (2002). Augmentation of drug reward by chronic food restriction: Behavioral evidence and underlying mechanisms. Physiology & Behavior, 76, 353–364. doi:10.1016/S0031-9384(02)00759-X.

    Article  CAS  Google Scholar 

  • Castaneda, A. E., Tuulio-Henriksson, A., Marttunen, M., Suvisaari, J., & Lönnqvist, J. (2008). A review on cognitive impairments in depressive and anxiety disorders with a focus on young adults. Journal of Affective Disorders, 106, 1–27. doi:10.1016/j.jad.2007.06.006.

    Article  PubMed  Google Scholar 

  • Chaki, S., Funakoshi, T., Hirota-Okuno, S., Nishiguchi, M., Shimazaki, T., Iijima, M., et al. (2005). Anxiolytic- and antidepressant-like profile of ATC0065 and ATC0175: Nonpeptidic and orally active melanin-concentrating hormone receptor 1 antagonists. The Journal of Pharmacology and Experimental Therapeutics, 313, 831–839. doi:10.1124/jpet.104.081711.

    Article  PubMed  CAS  Google Scholar 

  • Chefer, V. I., Czyzyk, T., Bolan, E. A., Moron, J., Pintar, J. E., & Shippenberg, T. S. (2005). Endogenous kappa-opioid receptor systems regulate mesoaccumbal dopamine dynamics and vulnerability to cocaine. The Journal of Neuroscience, 25, 5029–5037. doi:10.1523/JNEUROSCI.0854-05.2005.

    Article  PubMed  CAS  Google Scholar 

  • Chen, Y., Hu, C., Hsu, C. K., Zhang, Q., Bi, C., Asnicar, M., et al. (2002). Targeted disruption of the melanin-concentrating hormone receptor-1 results in hyperphagia and resistance to diet-induced obesity. Endocrinology, 143, 2469–2477. doi:10.1210/en.143.7.2469.

    Article  PubMed  CAS  Google Scholar 

  • Cryan, J. F., Valentino, R. J., & Lucki, I. (2005). Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neuroscience and Biobehavioral Reviews, 29, 547–569. doi:10.1016/j.neubiorev.2005.03.008.

    Article  PubMed  CAS  Google Scholar 

  • D'Aquila, P. S., Collu, M., Gessa, G. L., & Serra, G. (1997). Role of D1 and alpha1 receptors in the enhanced locomotor response to dopamine D2-like receptor stimulation induced by repeated electroconvulsive shock. Journal of Psychopharmacology (Oxford, England), 11, 41–44. doi:10.1177/026988119701100112.

    Article  Google Scholar 

  • David, D. J., Klemenhagen, K. C., Holick, K. A., Saxe, M. D., Mendez, I., Santarelli, L., et al. (2007). Efficacy of the MCHR1 antagonist N-[3-(1-{[4-(3, 4-difluorophenoxy) phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-methylpropanamide (SNAP 94847) in mouse models of anxiety and depression following acute and chronic administration is independent of hippocampal neurogenesis. The Journal of Pharmacology and Experimental Therapeutics, 321, 237–248. doi:10.1124/jpet.106.109678.

    Article  PubMed  CAS  Google Scholar 

  • DiLeone, R. J., Georgescu, D., & Nestler, E. J. (2003). Lateral hypothalamic neuropeptides in reward and drug addiction. Life Sciences, 73, 759–768. doi:10.1016/S0024-3205(03)00408-9.

    Article  PubMed  CAS  Google Scholar 

  • Duman, R. S., Malberg, J., & Thome, J. (1999). Neural plasticity to stress and antidepressant treatment. Biological Psychiatry, 46, 1181–1191. doi:10.1016/S0006-3223(99)00177-8.

    Article  PubMed  CAS  Google Scholar 

  • Flier, J. S., & Maratos-Flier, E. (1998). Obesity and the hypothalamus: Novel peptides for new pathways. Cell, 92, 437–440. doi:10.1016/S0092-8674(00)80937-X.

    Article  PubMed  CAS  Google Scholar 

  • Gehlert, D. R., Rasmussen, K., Shaw, J., Xia, L., Craft, L., Coskun, T., et al. (2009). Preclinical evaluation of melanin-concentrating hormone receptor 1 (MCHR1) antagonism for the treatment of obesity and depression. Journal of Pharmacology and Experimental Therapeutics, 329, 429–438.

    Article  PubMed  CAS  Google Scholar 

  • Georgescu, D., Sears, R. M., Hommel, J. D., Barrot, M., Bolanos, C. A., Marsh, D. J., et al. (2005). The hypothalamic neuropeptide melanin-concentrating hormone acts in the nucleus accumbens to modulate feeding behavior and forced-swim performance. The Journal of Neuroscience, 25, 2933–2940. doi:10.1523/JNEUROSCI.1714-04.2005.

    Article  PubMed  CAS  Google Scholar 

  • Gibson, W. T., Pissios, P., Trombly, D. J., Luan, J., Keogh, J., Wareham, N. J., et al. (2004). Melanin-concentrating hormone receptor mutations and human obesity: Functional analysis. Obesity Research, 12, 743–749. doi:10.1038/oby.2004.89.

    Article  PubMed  CAS  Google Scholar 

  • Gomori, A., Ishihara, A., Ito, M., Mashiko, S., Matsushita, H., Yumoto, M., et al. (2003). Chronic intracerebroventricular infusion of MCH causes obesity in mice. American Journal of Physiology. Endocrinology and Metabolism, 284, E583–E588.

    PubMed  CAS  Google Scholar 

  • Gonzalez, M. I., Vaziri, S., & Wilson, C. A. (1996). Behavioral effects of [alpha]-MSH and MCH after central administration in the female rat. Peptides, 17, 171–177. doi:10.1016/0196-9781(95)02092-6.

    Article  PubMed  CAS  Google Scholar 

  • Handlon, A. L., & Zhou, H. (2006). Melanin-concentrating hormone-1 receptor antagonists for the treatment of obesity. Journal of Medicinal Chemistry, 49, 4017–4022. doi:10.1021/jm058239j.

    Article  PubMed  CAS  Google Scholar 

  • Hanriot, L., Camargo, N., Courau, A. C., Leger, L., Luppi, P. H., & Peyron, C. (2007). Characterization of the melanin-concentrating hormone neurons activated during paradoxical sleep hypersomnia in rats. The Journal of Comparative Neurology, 505, 147–157. doi:10.1002/cne.21482.

    Article  PubMed  Google Scholar 

  • Hawes, B. E., Kil, E., Green, B., O'Neill, K., Fried, S., & Graziano, M. P. (2000). The melanin-concentrating hormone receptor couples to multiple G proteins to activate diverse intracellular signaling pathways. Endocrinology, 141, 4524–4532. doi:10.1210/en.141.12.4524.

    Article  PubMed  CAS  Google Scholar 

  • Hervieu, G. J., Cluderay, J. E., Harrison, D., Meakin, J., Maycox, P., Nasir, S., et al. (2000). The distribution of the mRNA and protein products of the melanin-concentrating hormone (MCH) receptor gene, slc-1, in the central nervous system of the rat. The European Journal of Neuroscience, 12, 1194–1216. doi:10.1046/j.1460-9568.2000.00008.x.

    Article  PubMed  CAS  Google Scholar 

  • Hill, J., Duckworth, M., Murdock, P., Rennie, G., Sabido-David, C., Ames, R. S., et al. (2001). Molecular cloning and functional characterization of MCH2, a novel human MCH receptor. The Journal of Biological Chemistry, 276, 20125–20129. doi:10.1074/jbc.M102068200.

    Article  PubMed  CAS  Google Scholar 

  • Hu, E. X., Wos, J. A., Dowty, M. E., Suchanek, P. M., Ji, W., Chambers, J. B., et al. (2008). Small-molecule melanin-concentrating hormone-1 receptor antagonists require brain penetration for inhibition of food intake and reduction in body weight. The Journal of Pharmacology and Experimental Therapeutics, 324, 206–213.

    CAS  Google Scholar 

  • Huang, C. Q., Baker, T., Schwarz, D., Fan, J., Heise, C. E., Zhang, M., et al. (2005). 1-(4-Amino-phenyl)-pyrrolidin-3-yl-amine and 6-(3-amino-pyrrolidin-1-yl)-pyridin-3-yl-amine derivatives as melanin-concentrating hormone receptor-1 antagonists. Bioorganic & Medicinal Chemistry Letters, 15, 3701–3706. doi:10.1016/j.bmcl.2005.05.130.

    Article  CAS  Google Scholar 

  • Hutchinson, N. I., & Ryder, S. W. (2007). Obesity pharmacotherapy from a regulatory perspective: Overview and key challenges. Clinical Pharmacology and Therapeutics, 81, 756–760. doi:10.1038/sj.clpt.6100169.

    Article  PubMed  CAS  Google Scholar 

  • Jeon, J. Y., Bradley, R. L., Kokkotou, E. G., Marino, F. E., Wang, X., Pissios, P., et al. (2006). MCH−/− mice are resistant to aging-associated increases in body weight and insulin resistance. Diabetes, 55, 428–434. doi:10.2337/diabetes.55.02.06.db05-0203.

    Article  PubMed  CAS  Google Scholar 

  • Jezova, D., Bartanusz, V., Westergren, I., Johansson, B. B., Rivier, J., Vale, W., et al. (1992). Rat melanin-concentrating hormone stimulates adrenocorticotropin secretion: Evidence for a site of action in brain regions protected by the blood–brain barrier. Endocrinology, 130, 1024–1029. doi:10.1210/en.130.2.1024.

    Article  PubMed  CAS  Google Scholar 

  • Kela, J., Salmi, P., Rimondini-Giorgini, R., Heilig, M., & Wahlestedt, C. (2003). Behavioural analysis of melanin-concentrating hormone in rats: Evidence for orexigenic and anxiolytic properties. Regulatory Peptides, 114, 109–114. doi:10.1016/S0167-0115(03)00114-9.

    Article  PubMed  CAS  Google Scholar 

  • Kennedy, A. R., Todd, J. F., Dhillo, W. S., Seal, L. J., Ghatei, M. A., O'Toole, C. P., et al. (2003). Effect of direct injection of melanin-concentrating hormone into the paraventricular nucleus: Further evidence for a stimulatory role in the adrenal axis via SLC-1. Journal of Neuroendocrinology, 15, 268–272. doi:10.1046/j.1365-2826.2003.00997.x.

    Article  PubMed  CAS  Google Scholar 

  • Kim, N., Meyers, K. M., Mendez-Andino, J. L., Warshakoon, N. C., Ji, W., Wos, J. A., et al. (2006). Identification of substituted 4-aminopiperidines and 3-aminopyrrolidines as potent MCH-R1 antagonists for the treatment of obesity. Bioorganic & Medicinal Chemistry Letters, 16, 5445–5450. doi:10.1016/j.bmcl.2006.07.053.

    Article  CAS  Google Scholar 

  • Kokkotou, E., Jeon, J. Y., Wang, X., Marino, F. E., Carlson, M., Trombly, D. J., et al. (2005). Mice with MCH ablation resist diet-induced obesity through strain-specific mechanisms. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 289, R117–R124. doi:10.1152/ajpregu.00861.2004.

    PubMed  CAS  Google Scholar 

  • Kolakowski, L. F., Jung, B. P., Nguyen, T., Johnson, M. P., Lynch, K. R., Cheng, R., et al. (1996). Characterization of a human gene related to genes encoding somatostatin receptors. FEBS Letters, 398, 253–258. doi:10.1016/S0014-5793(96)01160-X.

    Article  PubMed  CAS  Google Scholar 

  • Lalonde, R., & Qian, S. (2007). Exploratory activity, motor coordination, and spatial learning in Mchr1 knockout mice. Behavioural Brain Research, 178, 293–304. doi:10.1016/j.bbr.2007.01.006.

    Article  PubMed  CAS  Google Scholar 

  • Li, X., Tizzano, J. P., Griffey, K., Clay, M., Lindstrom, T., & Skolnick, P. (2001). Antidepressant-like actions of an AMPA receptor potentiator (LY392098). Neuropharmacology, 40, 1028–1033. doi:10.1016/S0028-3908(00)00194-5.

    Article  PubMed  CAS  Google Scholar 

  • Ludwig, D. S., Mountjoy, K. G., Tatro, J. B., Gillette, J. A., Frederich, R. C., Flier, J. S., et al. (1998). Melanin-concentrating hormone: A functional melanocortin antagonist in the hypothalamus. The American Journal of Physiology, 274, E627–E633.

    PubMed  CAS  Google Scholar 

  • Ludwig, D. S., Tritos, N. A., Mastaitis, J. W., Kulkarni, R., Kokkotou, E., Elmquist, J., et al. (2001). Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. The Journal of Clinical Investigation, 107, 379–386. doi:10.1172/JCI10660.

    Article  PubMed  CAS  Google Scholar 

  • Macdonald, D., Murgolo, N., Zhang, R., Durkin, J. P., Yao, X., Strader, C. D., et al. (2000). Molecular characterization of the melanin-concentrating hormone/receptor complex: Identification of critical residues involved in binding and activation. Molecular Pharmacology, 58, 217–225.

    PubMed  CAS  Google Scholar 

  • Mague, S. D., Pliakas, A. M., Todtenkopf, M. S., Tomasiewicz, H. C., Zhang, Y., Stevens, W. C., Jr., et al. (2003). Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats. The Journal of Pharmacology and Experimental Therapeutics, 305, 323–330. doi:10.1124/jpet.102.046433.

    Article  PubMed  CAS  Google Scholar 

  • Malberg, J. E., Eisch, A. J., Nestler, E. J., & Duman, R. S. (2000). Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. The Journal of Neuroscience, 20, 9104–9110.

    PubMed  CAS  Google Scholar 

  • Marsh, D. J., Weingarth, D. T., Novi, D. E., Chen, H. Y., Trumbauer, M. E., Chen, A. S., et al. (2002). Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proceedings of the National Academy of Sciences of the United States of America, 99, 3240–3245. doi:10.1073/pnas.052706899.

    Article  PubMed  CAS  Google Scholar 

  • McEwen, B. S. (2003). Mood disorders and allostatic load. Biological Psychiatry, 54, 200–207. doi:10.1016/S0006-3223(03)00177-X.

    Article  PubMed  Google Scholar 

  • Millan, M. J., Gobert, A., Panayi, F., Rivet, J. M., Dekeyne, A., Brocco, M., et al. (2008). The melanin-concentrating hormone1 receptor antagonists, SNAP-7941 and GW3430, enhance social recognition and dialysate levels of acetylcholine in the frontal cortex of rats. The International Journal of Neuropsychopharmacology, 11, 1105–1122. doi:10.1017/S1461145708008894.

    Article  PubMed  CAS  Google Scholar 

  • Monzon, M. E., & De Barioglio, S. R. (1999). Response to novelty after i.c.v. injection of melanin-concentrating hormone (MCH) in rats. Physiology & Behavior, 67, 813–817. doi:10.1016/S0031-9384(99)00117-1.

    Article  CAS  Google Scholar 

  • Monzon, M. E., de Souza, M. M., Izquierdo, L. A., Izquierdo, I., Barros, D. M., & de Barioglio, S. R. (1999). Melanin-concentrating hormone (MCH) modifies memory retention in rats. Peptides, 20, 1517–1519. doi:10.1016/S0196-9781(99)00164-3.

    Article  PubMed  CAS  Google Scholar 

  • Mori, M., Harada, M., Terao, Y., Sugo, T., Watanabe, T., Shimomura, Y., et al. (2001). Cloning of a novel G protein-coupled receptor, SLT, a subtype of the melanin-concentrating hormone receptor. Biochemical and Biophysical Research Communications, 283, 1013–1018. doi:10.1006/bbrc.2001.4893.

    Article  PubMed  CAS  Google Scholar 

  • Navarra, P., Tsagarakis, S., Coy, D. H., Rees, L. H., Besser, G. M., & Grossman, A. B. (1990). Rat melanin concentrating hormone does not modify the release of CRH-41 from rat hypothalamus or ACTH from the anterior pituitary in vitro. The Journal of Endocrinology, 127, R1–R4. doi:10.1677/joe.0.127R001.

    Article  PubMed  Google Scholar 

  • Nestler, E. J. (2001). Molecular neurobiology of addiction. The American Journal on Addictions, 10, 201–217. doi:10.1080/105504901750532094.

    Article  PubMed  CAS  Google Scholar 

  • Pissios, P., & Maratos-Flier, E. (2003). Melanin-concentrating hormone: From fish skin to skinny mammals. Trends in Endocrinology and Metabolism, 14, 243–248. doi:10.1016/S1043-2760(03)00079-1.

    Article  PubMed  CAS  Google Scholar 

  • Pissios, P., Trombly, D. J., Tzameli, I., & Maratos-Flier, E. (2003). Melanin-concentrating hormone receptor 1 activates extracellular signal-regulated kinase and synergizes with G(s)-coupled pathways. Endocrinology, 144, 3514–3523. doi:10.1210/en.2002-0004.

    Article  PubMed  CAS  Google Scholar 

  • Pissios, P., Bradley, R. L., & Maratos-Flier, E. (2006). Expanding the scales: The multiple roles of MCH in regulating energy balance and other biological functions. Endocrine Reviews, 27, 606–620. doi:10.1210/er.2006-0021.

    Article  PubMed  CAS  Google Scholar 

  • Pissios, P., Ozcan, U., Kokkotou, E., Okada, T., Liew, C. W., Liu, S., et al. (2007). Melanin concentrating hormone is a novel regulator of islet function and growth. Diabetes, 56, 311–319. doi:10.2337/db06-0708.

    Article  PubMed  CAS  Google Scholar 

  • Presse, F., Hervieu, G., Imaki, T., Sawchenko, P. E., Vale, W., & Nahon, J. L. (1992). Rat melanin-concentrating hormone messenger ribonucleic acid expression: Marked changes during development and after stress and glucocorticoid stimuli. Endocrinology, 131, 1241–1250. doi:10.1210/en.131.3.1241.

    Article  PubMed  CAS  Google Scholar 

  • Qu, D., Ludwig, D. S., Gammeltoft, S., Piper, M., Pelleymounter, M. A., Cullen, M. J., et al. (1996). A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Nature, 380, 243–247. doi:10.1038/380243a0.

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez, M., Beauverger, P., Naime, I., Rique, H., Ouvry, C., Souchaud, S., et al. (2001). Cloning and molecular characterization of the novel human melanin-concentrating hormone receptor MCH2. Molecular Pharmacology, 60, 632–639.

    PubMed  CAS  Google Scholar 

  • Rossi, M., Choi, S. J., O'Shea, D., Miyoshi, T., Ghatei, M. A., & Bloom, S. R. (1997). Melanin-concentrating hormone acutely stimulates feeding, but chronic administration has no effect on body weight. Endocrinology, 138, 351–355. doi:10.1210/en.138.1.351.

    Article  PubMed  CAS  Google Scholar 

  • Roy, M., David, N. K., Danao, J. V., Baribault, H., Tian, H., & Giorgetti, M. (2006). Genetic inactivation of melanin-concentrating hormone receptor subtype 1 (MCHR1) in mice exerts anxiolytic-like behavioral effects. Neuropsychopharmacology, 31, 112–120.

    PubMed  CAS  Google Scholar 

  • Roy, M., David, N., Cueva, M., & Giorgetti, M. (2007). A study of the involvement of melanin-concentrating hormone receptor 1 (MCHR1) in murine models of depression. Biological Psychiatry, 61, 174–180. doi:10.1016/j.biopsych.2006.03.076.

    Article  PubMed  CAS  Google Scholar 

  • Rutanen, J., Pihlajamaki, J., Vanttinen, M., Salmenniemi, U., Ruotsalainen, E., Kuulasmaa, T., et al. (2007). Single nucleotide polymorphisms of the MCHR1 gene do not affect metabolism in humans. Obesity (Silver Spring, Md.), 15, 2902–2907. doi:10.1038/oby.2007.345.

    Article  CAS  Google Scholar 

  • Sailer, A. W., Sano, H., Zeng, Z., McDonald, T. P., Pan, J., Pong, S.-S., et al. (2001). Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R. Proceedings of the National Academy of Sciences of the United States of America, 98, 7564–7569. doi:10.1073/pnas.121170598.

    Article  PubMed  CAS  Google Scholar 

  • Saito, Y., Cheng, M., Leslie, F. M., & Civelli, O. (2001). Expression of the melanin-concentrating hormone (MCH) receptor mRNA in the rat brain. The Journal of Comparative Neurology, 435, 26–40. doi:10.1002/cne.1191.

    Article  PubMed  CAS  Google Scholar 

  • Saito, Y., Tetsuka, M., Yue, L., Kawamura, Y., & Maruyama, K. (2003). Functional role of N-linked glycosylation on the rat melanin-concentrating hormone receptor 1. FEBS Letters, 533, 29–34. doi:10.1016/S0014-5793(02)03744-4.

    Article  PubMed  CAS  Google Scholar 

  • Santarelli, L., Saxe, M., Gross, C., Surget, A., Battaglia, F., Dulawa, S., et al. (2003). Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science, 301, 805–809. doi:10.1126/science.1083328.

    Article  PubMed  CAS  Google Scholar 

  • Serra, G., Collu, M., D'Aquila, P. S., & Gessa, G. L. (1992). Role of the mesolimbic dopamine system in the mechanism of action of antidepressants. Pharmacology & Toxicology, 71(Suppl 1), 72–85. doi:10.1111/j.1600-0773.1992.tb01631.x.

    Article  CAS  Google Scholar 

  • Shearman, L. P., Camacho, R. E., Sloan Stribling, D., Zhou, D., Bednarek, M. A., Hreniuk, D. L., et al. (2003). Chronic MCH-1 receptor modulation alters appetite, body weight and adiposity in rats. European Journal of Pharmacology, 475, 37–47. doi:10.1016/S0014-2999(03)02146-0.

    Article  PubMed  CAS  Google Scholar 

  • Shimada, M., Tritos, N. A., Lowell, B. B., Flier, J. S., & Maratos-Flier, E. (1998). Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature, 396, 670–674. doi:10.1038/25341.

    Article  PubMed  CAS  Google Scholar 

  • Shirayama, Y., Ishida, H., Iwata, M., Hazama, G. I., Kawahara, R., & Duman, R. S. (2004). Stress increases dynorphin immunoreactivity in limbic brain regions and dynorphin antagonism produces antidepressant-like effects. Journal of Neurochemistry, 90, 1258–1268. doi:10.1111/j.1471-4159.2004.02589.x.

    Article  PubMed  CAS  Google Scholar 

  • Skofitsch, G., Jacobowitz, D. M., & Zamir, N. (1985). Immunohistochemical localization of a melanin concentrating hormone-like peptide in the rat brain. Brain Research Bulletin, 15, 635–649. doi:10.1016/0361-9230(85)90213-8.

    Article  PubMed  CAS  Google Scholar 

  • Smith, D. G., Tzavara, E. T., Shaw, J., Luecke, S., Wade, M., Davis, R., et al. (2005). Mesolimbic dopamine super-sensitivity in melanin-concentrating hormone-1 receptor-deficient mice. The Journal of Neuroscience, 25, 914–922. doi:10.1523/JNEUROSCI.4079-04.2005.

    Article  PubMed  CAS  Google Scholar 

  • Smith, D. G., Davis, R. J., Rorick-Kehn, L., Morin, M., Witkin, J. M., McKinzie, D. L., et al. (2006). Melanin-concentrating hormone-1 receptor modulates neuroendocrine, behavioral, and corticolimbic neurochemical stress responses in mice. Neuropsychopharmacology, 31, 1135–1145. doi:10.1038/sj.npp. 1300881.

    Article  PubMed  CAS  Google Scholar 

  • Smith, D. G., Qi, H., Svenningsson, P., Wade, M., Davis, R. J., Gehlert, D. R., et al. (2008). Behavioral and biochemical responses to d-amphetamine in MCH1 receptor knockout mice. Synapse (New York, N.Y.), 62, 128–136. doi:10.1002/syn.20473.

    CAS  Google Scholar 

  • Smith, D. G., Hegde, L. G., Wolinsky, T. D., Miller, S., Papp, M., Ping, X., et al. (2009). The effects of stressful stimuli and hypothalamic-pituitary-adrenal axis activation are reversed by the melanin-concentrating hormone 1 receptor antagonist SNAP 94847 in rodents. Behavioural Brain Research, 197, 284–291. doi:10.1016/j.bbr.2008.08.026.

    Article  PubMed  CAS  Google Scholar 

  • Sotak, B. N., Hnasko, T. S., Robinson, S., Kremer, E. J., & Palmiter, R. D. (2005). Dysregulation of dopamine signaling in the dorsal striatum inhibits feeding. Brain Research, 1061, 88–96. doi:10.1016/j.brainres.2005.08.053.

    Article  PubMed  CAS  Google Scholar 

  • Spanagel, R., Herz, A., & Shippenberg, T. S. (1992). Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proceedings of the National Academy of Sciences of the United States of America, 89, 2046–2050. doi:10.1073/pnas.89.6.2046.

    Article  PubMed  CAS  Google Scholar 

  • Suzuki, M., Narnaware, Y. K., Baker, B. I., & Levy, A. (1995). Influence of environmental colour and diurnal phase on MCH gene expression in the trout. Journal of Neuroendocrinology, 7, 319–328. doi:10.1111/j.1365-2826.1995.tb00764.x.

    Article  PubMed  CAS  Google Scholar 

  • Svenningsson, P., Tzavara, E. T., Witkin, J. M., Fienberg, A. A., Nomikos, G. G., & Greengard, P. (2002). Involvement of striatal and extrastriatal DARPP-32 in biochemical and behavioral effects of fluoxetine (Prozac). Proceedings of the National Academy of Sciences of the United States of America, 99, 3182–3187. doi:10.1073/pnas.052712799.

    Article  PubMed  CAS  Google Scholar 

  • Swanson, L. W., & Petrovich, G. D. (1998). What is the amygdala? Trends in Neurosciences, 21, 323–331. doi:10.1016/S0166-2236(98)01265-X.

    Article  PubMed  CAS  Google Scholar 

  • Takekawa, S., Asami, A., Ishihara, Y., Terauchi, J., Kato, K., Shimomura, Y., et al. (2002). T-226296: A novel, orally active and selective melanin-concentrating hormone receptor antagonist. European Journal of Pharmacology, 438, 129–135. doi:10.1016/S0014-2999(02)01314-6.

    Article  PubMed  CAS  Google Scholar 

  • Tritos, N. A., & Maratos-Flier, E. (1999). Two important systems in energy homeostasis: Melanocortins and melanin-concentrating hormone. Neuropeptides, 33, 339–349. doi:10.1054/npep.1999.0055.

    Article  PubMed  CAS  Google Scholar 

  • Varas, M. M., Perez, M. F., Ramirez, O. A., & de Barioglio, S. R. (2003). Increased susceptibility to LTP generation and changes in NMDA-NR1 and -NR2B subunits mRNA expression in rat hippocampus after MCH administration. Peptides, 24, 1403–1411. doi:10.1016/j.peptides.2003.09.006.

    Article  PubMed  CAS  Google Scholar 

  • Wang, S., Bihan, J., O'Neill, K., Weig, B., Fried, S., Laz, T., et al. (2001). Identification and pharmacological characterization of a novel human melanin-concentrating hormone receptor, MCH-R2. The Journal of Biological Chemistry, 276, 34664–34670. doi:10.1074/jbc.M102601200.

    Article  PubMed  CAS  Google Scholar 

  • Wermter, A. K., Reichwald, K., Buch, T., Geller, F., Platzer, C., Huse, K., et al. (2005). Mutation analysis of the MCHR1 gene in human obesity. European Journal of Endocrinology, 152, 851–862. doi:10.1530/eje.1.01917.

    Article  PubMed  CAS  Google Scholar 

  • Willner, P., Hale, A. S., & Argyropoulos, S. (2005). Dopaminergic mechanism of antidepressant action in depressed patients. Journal of Affective Disorders, 86, 37–45. doi:10.1016/j.jad.2004.12.010.

    Article  PubMed  CAS  Google Scholar 

  • Zhou, D., Shen, Z., Strack, A. M., Marsh, D. J., & Shearman, L. P. (2005). Enhanced running wheel activity of both Mch1r- and Pmch-deficient mice. Regulatory Peptides, 124, 53–63. doi:10.1016/j.regpep.2004.06.026.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Wyeth Research, CN 8000, Princeton, NJ, 08540, USA

    Ildiko Antal-Zimanyi & Xavier Khawaja

Authors
  1. Ildiko Antal-Zimanyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xavier Khawaja
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ildiko Antal-Zimanyi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Antal-Zimanyi, I., Khawaja, X. The Role of Melanin-Concentrating Hormone in Energy Homeostasis and Mood Disorders. J Mol Neurosci 39, 86–98 (2009). https://doi.org/10.1007/s12031-009-9207-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-009-9207-6

Keywords

Search

Navigation