This Article Full Text Full Text (PDF) All Versions of this Article: 144/9/3943    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Abbott, C. R. Articles by Bloom, S. R. Search for Related Content PubMed PubMed Citation Articles by Abbott, C. R. Articles by Bloom, S. R.

Identification of Hypothalamic Nuclei Involved in the Orexigenic Effect of Melanin-Concentrating Hormone

Endocrine Unit, Imperial College London, Hammersmith Campus, London W12 ONN, United Kingdom

Address all correspondence and requests for reprints to: Professor S. R. Bloom, Endocrine Unit, Imperial College London, 6th Floor Commonwealth Building, Hammersmith Campus, Du Cane Road, London W12 0NN, United Kingdom. E-mail: s.bloom{at}imperial.ac.uk.

The hypothalamic neuropeptide melanin-concentrating hormone (MCH) increases feeding when injected intracerebroventricularly in rats. To identify the hypothalamic nuclei responsible for the orexigenic effect, we injected the peptide into discrete hypothalamic nuclei known to express the MCH receptor, MCH1R. MCH (0.6 nmol) elicited a rapid and significant increase in feeding in satiated rats following injection into the arcuate nucleus (0–1 h: 421 ± 60%; P < 0.01). An elevation in feeding was also observed following injection into the paraventricular nucleus, which was sustained up to 4 h post injection (0–4 h: 218 ± 29%; P < 0.01). A significant increase in feeding during this time period was also observed following injection into the dorsomedial nucleus (0–4 h: 155 ± 12%; P < 0.05). No significant alteration in feeding was observed following injection into the supraoptic nucleus, lateral hypothalamic area, medial preoptic area, anterior hypothalamic area, or ventromedial nucleus of the hypothalamus. To identify the neurotransmitters that may be potentially involved in this effect, we examined their release from hypothalamic explants in vitro following exogenous MCH administration. MCH (1 µM) increased the release of the orexigenic neurotransmitters neuropeptide Y (37.8 ± 6.0 fmol/explant vs. basal 30.2 ± 4.3 fmol/explant; P < 0.05) and agouti-related peptide (4.1 ± 0.6 fmol/explant vs. basal 2.4 ± 0.2 fmol/explant; P < 0.05) and decreased the release of the anorectic neurotransmitters -MSH (41.7 ± 6.8 fmol/explant vs. basal 65.9 ± 11.0 fmol/explant; P < 0.01) and cocaine- and amphetamine-regulated transcript (112.3 ± 12.4 fmol/explant vs. basal 167.4 ± 13.0 fmol/explant; P < 0.001). These studies suggest that the orexigenic effect of MCH may be mediated via activation or inhibition of these feeding circuits within the arcuate nucleus and paraventricular nucleus of the hypothalamus.

This article has been cited by other articles:

				J.-P. Baird, C. Rios, J. L. Loveland, J. Beck, A. Tran, and C. E. Mahoney Effects of hindbrain melanin-concentrating hormone and neuropeptide Y administration on licking for water, saccharin, and sucrose solutions Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R329 - R343. [Abstract] [Full Text] [PDF]

				M. Ghoussaini, V. Vatin, C. Lecoeur, V. Abkevich, A. Younus, C. Samson, C. Wachter, B. Heude, M. Tauber, P. Tounian, et al. Genetic Study of the Melanin-Concentrating Hormone Receptor 2 in Childhood and Adulthood Severe Obesity J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4403 - 4409. [Abstract] [Full Text] [PDF]

				B. M. McGowan, S. A. Stanley, N. E. White, A. Spangeus, M. Patterson, E. L. Thompson, K. L. Smith, J. Donovan, J. V. Gardiner, M. A. Ghatei, et al. Hypothalamic mapping of orexigenic action and Fos-like immunoreactivity following relaxin-3 administration in male Wistar rats Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E913 - E919. [Abstract] [Full Text] [PDF]

				J.-P. Baird, C. Rios, N. E. Gray, C. E. Walsh, S. G. Fischer, and A. L. Pecora Effects of melanin-concentrating hormone on licking microstructure and brief-access taste responses Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2006; 291(5): R1265 - R1274. [Abstract] [Full Text] [PDF]

				P. Pissios, R. L. Bradley, and E. Maratos-Flier Expanding the Scales: The Multiple Roles of MCH in Regulating Energy Balance and Other Biological Functions Endocr. Rev., October 1, 2006; 27(6): 606 - 620. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. N. Roemmich, E. J. Richmond, and C. Y. Bowers Somatotropic and Gonadotropic Axes Linkages in Infancy, Childhood, and the Puberty-Adult Transition Endocr. Rev., April 1, 2006; 27(2): 101 - 140. [Abstract] [Full Text] [PDF]

				U. A. Unmehopa, J. J. van Heerikhuize, W. Spijkstra, J. W. Woods, A. D. Howard, E. Zycband, S. D. Feighner, D. L. Hreniuk, O. C. Palyha, X.-M. Guan, et al. Increased Melanin Concentrating Hormone Receptor Type I in the Human Hypothalamic Infundibular Nucleus in Cachexia J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2412 - 2419. [Abstract] [Full Text] [PDF]

				D. Georgescu, R. M. Sears, J. D. Hommel, M. Barrot, C. A. Bolanos, D. J. Marsh, M. A. Bednarek, J. A. Bibb, E. Maratos-Flier, E. J. Nestler, et al. The Hypothalamic Neuropeptide Melanin-Concentrating Hormone Acts in the Nucleus Accumbens to Modulate Feeding Behavior and Forced-Swim Performance J. Neurosci., March 16, 2005; 25(11): 2933 - 2940. [Abstract] [Full Text] [PDF]

				W. M. Kong, N. M. Martin, K. L. Smith, J. V. Gardiner, I. P. Connoley, D. A. Stephens, W. S. Dhillo, M. A. Ghatei, C. J. Small, and S. R. Bloom Triiodothyronine Stimulates Food Intake via the Hypothalamic Ventromedial Nucleus Independent of Changes in Energy Expenditure Endocrinology, November 1, 2004; 145(11): 5252 - 5258. [Abstract] [Full Text] [PDF]

				A. Astrand, M. Bohlooly-Y, S. Larsdotter, M. Mahlapuu, H. Andersen, J. Tornell, C. Ohlsson, M. Snaith, and D. G. A. Morgan Mice lacking melanin-concentrating hormone receptor 1 demonstrate increased heart rate associated with altered autonomic activity Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2004; 287(4): R749 - R758. [Abstract] [Full Text] [PDF]

				D. L. Drazen, L. M. Coolen, A. D. Strader, M. D. Wortman, S. C. Woods, and R. J. Seeley Differential Effects of Adrenalectomy on Melanin-Concentrating Hormone and Orexin A Endocrinology, July 1, 2004; 145(7): 3404 - 3412. [Abstract] [Full Text] [PDF]