IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0019600.html
   My bibliography  Save this article

Chronic Loss of Melanin-Concentrating Hormone Affects Motivational Aspects of Feeding in the Rat

Author

Listed:
  • Joram D Mul
  • Susanne E la Fleur
  • Pim W Toonen
  • Anthonieke Afrasiab-Middelman
  • Rob Binnekade
  • Dustin Schetters
  • Michel M M Verheij
  • Robert M Sears
  • Judith R Homberg
  • Anton N M Schoffelmeer
  • Roger A H Adan
  • Ralph J DiLeone
  • Taco J De Vries
  • Edwin Cuppen

Abstract

Current epidemic obesity levels apply great medical and financial pressure to the strenuous economy of obesity-prone cultures, and neuropeptides involved in body weight regulation are regarded as attractive targets for a possible treatment of obesity in humans. The lateral hypothalamus and the nucleus accumbens shell (AcbSh) form a hypothalamic-limbic neuropeptide feeding circuit mediated by Melanin-Concentrating Hormone (MCH). MCH promotes feeding behavior via MCH receptor-1 (MCH1R) in the AcbSh, although this relationship has not been fully characterized. Given the AcbSh mediates reinforcing properties of food, we hypothesized that MCH modulates motivational aspects of feeding. Here we show that chronic loss of the rat MCH-precursor Pmch decreased food intake predominantly via a reduction in meal size during rat development and reduced high-fat food-reinforced operant responding in adult rats. Moreover, acute AcbSh administration of Neuropeptide-GE and Neuropeptide-EI (NEI), both additional neuropeptides derived from Pmch, or chronic intracerebroventricular infusion of NEI, did not affect feeding behavior in adult pmch+/+ or pmch−/− rats. However, acute administration of MCH to the AcbSh of adult pmch−/− rats elevated feeding behavior towards wild type levels. Finally, adult pmch−/− rats showed increased ex vivo electrically evoked dopamine release and increased limbic dopamine transporter levels, indicating that chronic loss of Pmch in the rat affects the limbic dopamine system. Our findings support the MCH-MCH1R system as an amplifier of consummatory behavior, confirming this system as a possible target for the treatment of obesity. We propose that MCH-mediated signaling in the AcbSh positively mediates motivational aspects of feeding behavior. Thereby it provides a crucial signal by which hypothalamic neural circuits control energy balance and guide limbic brain areas to enhance motivational or incentive-related aspects of food consumption.

Suggested Citation

  • Joram D Mul & Susanne E la Fleur & Pim W Toonen & Anthonieke Afrasiab-Middelman & Rob Binnekade & Dustin Schetters & Michel M M Verheij & Robert M Sears & Judith R Homberg & Anton N M Schoffelmeer & R, 2011. "Chronic Loss of Melanin-Concentrating Hormone Affects Motivational Aspects of Feeding in the Rat," PLOS ONE, Public Library of Science, vol. 6(5), pages 1-13, May.
    • Handle: RePEc:plo:pone00:0019600
    DOI: 10.1371/journal.pone.0019600
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019600
    Download Restriction: no
    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0019600&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pone.0019600?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Masako Shimada & Nicholas A. Tritos & Bradford B. Lowell & Jeffrey S. Flier & Eleftheria Maratos-Flier, 1998. "Mice lacking melanin-concentrating hormone are hypophagic and lean," Nature, Nature, vol. 396(6712), pages 670-674, December.
    2. Jose P. Silva & Ferdinand von Meyenn & Jessica Howell & Bernard Thorens & Christian Wolfrum & Markus Stoffel, 2009. "Regulation of adaptive behaviour during fasting by hypothalamic Foxa2," Nature, Nature, vol. 462(7273), pages 646-650, December.
    3. Jon Chambers & Robert S. Ames & Derk Bergsma & Alison Muir & Laura R. Fitzgerald & Guillaume Hervieu & George M. Dytko & James J. Foley & John Martin & Wu-Schyong Liu & Janet Park & Catherine Ellis & , 1999. "Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1," Nature, Nature, vol. 400(6741), pages 261-265, July.
    4. Glenda C. Harris & Mathieu Wimmer & Gary Aston-Jones, 2005. "A role for lateral hypothalamic orexin neurons in reward seeking," Nature, Nature, vol. 437(7058), pages 556-559, September.
    5. Yumiko Saito & Hans-Peter Nothacker & Zhiwei Wang & Steven H. S. Lin & Frances Leslie & Olivier Civelli, 1999. "Molecular characterization of the melanin-concentrating-hormone receptor," Nature, Nature, vol. 400(6741), pages 265-269, July.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Kenkichi Takase & Kenichi Kikuchi & Yousuke Tsuneoka & Satoko Oda & Masaru Kuroda & Hiromasa Funato, 2014. "Meta-Analysis of Melanin-Concentrating Hormone Signaling-Deficient Mice on Behavioral and Metabolic Phenotypes," PLOS ONE, Public Library of Science, vol. 9(6), pages 1-15, June.
    2. Keshav S. Subramanian & Logan Tierno Lauer & Anna M. R. Hayes & Léa Décarie-Spain & Kara McBurnett & Anna C. Nourbash & Kristen N. Donohue & Alicia E. Kao & Alexander G. Bashaw & Denis Burdakov & Emil, 2023. "Hypothalamic melanin-concentrating hormone neurons integrate food-motivated appetitive and consummatory processes in rats," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Robyn Mary Brown & Jennifer Lynn Short & Andrew John Lawrence, 2010. "Identification of Brain Nuclei Implicated in Cocaine-Primed Reinstatement of Conditioned Place Preference: A Behaviour Dissociable from Sensitization," PLOS ONE, Public Library of Science, vol. 5(12), pages 1-13, December.
    4. Huan Sheng & Chao Lei & Yu Yuan & Yali Fu & Dongyang Cui & Li Yang & Da Shao & Zixuan Cao & Hao Yang & Xinli Guo & Chenshan Chu & Yaxian Wen & Zhangyin Cai & Ming Chen & Bin Lai & Ping Zheng, 2023. "Nucleus accumbens circuit disinhibits lateral hypothalamus glutamatergic neurons contributing to morphine withdrawal memory in male mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Ines Villano & Marco La Marra & Girolamo Di Maio & Vincenzo Monda & Sergio Chieffi & Ezia Guatteo & Giovanni Messina & Fiorenzo Moscatelli & Marcellino Monda & Antonietta Messina, 2022. "Physiological Role of Orexinergic System for Health," IJERPH, MDPI, vol. 19(14), pages 1-18, July.
    6. Atsushi Noritake & Taihei Ninomiya & Kenta Kobayashi & Masaki Isoda, 2023. "Chemogenetic dissection of a prefrontal-hypothalamic circuit for socially subjective reward valuation in macaques," Nature Communications, Nature, vol. 14(1), pages 1-9, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0019600. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.