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

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,...

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Veröffentlicht in:Endocrinology (Philadelphia) 2003-09, Vol.144 (9), p.3943-3949
Hauptverfasser: Abbott, Caroline R, Kennedy, Adam R, Wren, Alison M, Rossi, Michela, Murphy, Kevin G, Seal, Leighton J, Todd, Jeannie F, Ghatei, Mohammad A, Small, Caroline J, Bloom, Stephen R
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container_issue 9
container_start_page 3943
container_title Endocrinology (Philadelphia)
container_volume 144
creator Abbott, Caroline R
Kennedy, Adam R
Wren, Alison M
Rossi, Michela
Murphy, Kevin G
Seal, Leighton J
Todd, Jeannie F
Ghatei, Mohammad A
Small, Caroline J
Bloom, Stephen R
description 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 α-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.
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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 α-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). 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Urophysis ; Injection ; Intercellular Signaling Peptides and Proteins ; Male ; Melanin ; Melanin-concentrating hormone ; Melanins - pharmacology ; Microinjections ; Neuropeptide Y ; Neuropeptide Y - metabolism ; Neuropeptides ; Neurotransmitters ; Nuclei ; Paraventricular Hypothalamic Nucleus - drug effects ; Paraventricular Hypothalamic Nucleus - metabolism ; Paraventricular nucleus ; Peptides ; Pituitary Hormones - pharmacology ; Preoptic area ; Preoptic area (medial) ; Proteins - metabolism ; Rats ; Rats, Wistar ; Supraoptic nucleus ; Vertebrates: endocrinology</subject><ispartof>Endocrinology (Philadelphia), 2003-09, Vol.144 (9), p.3943-3949</ispartof><rights>Copyright © 2003 by The Endocrine Society 2003</rights><rights>2004 INIST-CNRS</rights><rights>Copyright © 2003 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c525t-d86fdee8034204426df27628e1cfa0e9e7bc93ec3cc3bd3236095ec674344fc53</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=15064639$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12933668$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abbott, Caroline R</creatorcontrib><creatorcontrib>Kennedy, Adam R</creatorcontrib><creatorcontrib>Wren, Alison M</creatorcontrib><creatorcontrib>Rossi, Michela</creatorcontrib><creatorcontrib>Murphy, Kevin G</creatorcontrib><creatorcontrib>Seal, Leighton J</creatorcontrib><creatorcontrib>Todd, Jeannie F</creatorcontrib><creatorcontrib>Ghatei, Mohammad A</creatorcontrib><creatorcontrib>Small, Caroline J</creatorcontrib><creatorcontrib>Bloom, Stephen R</creatorcontrib><title>Identification of Hypothalamic Nuclei Involved in the Orexigenic Effect of Melanin-Concentrating Hormone</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description><![CDATA[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 α-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.]]></description><subject>Agouti-Related Protein</subject><subject>alpha-MSH - metabolism</subject><subject>Amphetamines</subject><subject>Animals</subject><subject>Appetite - drug effects</subject><subject>Appetite - physiology</subject><subject>Arcuate nucleus</subject><subject>Arcuate Nucleus of Hypothalamus - drug effects</subject><subject>Arcuate Nucleus of Hypothalamus - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cocaine</subject><subject>Cocaine- and amphetamine-regulated transcript protein</subject><subject>Eating - drug effects</subject><subject>Eating - physiology</subject><subject>Explants</subject><subject>Feeding</subject><subject>Feeding Behavior - drug effects</subject><subject>Feeding Behavior - physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hormones and neuropeptides. Regulation</subject><subject>Hypothalamic Hormones - pharmacology</subject><subject>Hypothalamus</subject><subject>Hypothalamus (anterior)</subject><subject>Hypothalamus (lateral)</subject><subject>Hypothalamus (medial)</subject><subject>Hypothalamus (ventromedial)</subject><subject>Hypothalamus. Hypophysis. Epiphysis. Urophysis</subject><subject>Injection</subject><subject>Intercellular Signaling Peptides and Proteins</subject><subject>Male</subject><subject>Melanin</subject><subject>Melanin-concentrating hormone</subject><subject>Melanins - pharmacology</subject><subject>Microinjections</subject><subject>Neuropeptide Y</subject><subject>Neuropeptide Y - metabolism</subject><subject>Neuropeptides</subject><subject>Neurotransmitters</subject><subject>Nuclei</subject><subject>Paraventricular Hypothalamic Nucleus - drug effects</subject><subject>Paraventricular Hypothalamic Nucleus - metabolism</subject><subject>Paraventricular nucleus</subject><subject>Peptides</subject><subject>Pituitary Hormones - pharmacology</subject><subject>Preoptic area</subject><subject>Preoptic area (medial)</subject><subject>Proteins - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Supraoptic nucleus</subject><subject>Vertebrates: endocrinology</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10Etr3DAUBWAREpJp0l3XxRDabupUL9vjZRnSzkAem2QtNNdXGQVbciU7JP8-MmMYKO1KCD6de3UI-cToFeOM_kB3xSkVOWWyPiILVssir1hFj8mCUibyivPqjHyI8TldpZTilJwxXgtRlssF2W0adIM1FvRgvcu8ydZvvR92utWdhexuhBZttnEvvn3BJrMuG3aY3Qd8tU_okrg2BmGYHt5iq511-co7SKEhJbqnbO1D5x1ekBOj24gf5_OcPP66flit85v735vVz5scCl4MebMsTYO4pEJyKiUvG8Orki-RgdEUa6y2UAsEASC2jeCipHWBUFZSSGmgEOfk6z63D_7PiHFQnY2AbVoN_RhVlV5QxkWCl3_BZz8Gl3ZTgglapH5kmdT3vYLgYwxoVB9sp8ObYlRN_St0aupfTf0n_nkOHbcdNgc8F57AlxnoCLo1QTuw8eAKOk2dgr7tnR_7_43M55FiL9E1HoJ12AeM8fCbfy76DklfqlM</recordid><startdate>20030901</startdate><enddate>20030901</enddate><creator>Abbott, Caroline R</creator><creator>Kennedy, Adam R</creator><creator>Wren, Alison M</creator><creator>Rossi, Michela</creator><creator>Murphy, Kevin G</creator><creator>Seal, Leighton J</creator><creator>Todd, Jeannie F</creator><creator>Ghatei, Mohammad A</creator><creator>Small, Caroline J</creator><creator>Bloom, Stephen R</creator><general>Endocrine Society</general><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20030901</creationdate><title>Identification of Hypothalamic Nuclei Involved in the Orexigenic Effect of Melanin-Concentrating Hormone</title><author>Abbott, Caroline R ; Kennedy, Adam R ; Wren, Alison M ; Rossi, Michela ; Murphy, Kevin G ; Seal, Leighton J ; Todd, Jeannie F ; Ghatei, Mohammad A ; Small, Caroline J ; Bloom, Stephen R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c525t-d86fdee8034204426df27628e1cfa0e9e7bc93ec3cc3bd3236095ec674344fc53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Agouti-Related Protein</topic><topic>alpha-MSH - metabolism</topic><topic>Amphetamines</topic><topic>Animals</topic><topic>Appetite - drug effects</topic><topic>Appetite - physiology</topic><topic>Arcuate nucleus</topic><topic>Arcuate Nucleus of Hypothalamus - drug effects</topic><topic>Arcuate Nucleus of Hypothalamus - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cocaine</topic><topic>Cocaine- and amphetamine-regulated transcript protein</topic><topic>Eating - drug effects</topic><topic>Eating - physiology</topic><topic>Explants</topic><topic>Feeding</topic><topic>Feeding Behavior - drug effects</topic><topic>Feeding Behavior - physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hormones and neuropeptides. Regulation</topic><topic>Hypothalamic Hormones - pharmacology</topic><topic>Hypothalamus</topic><topic>Hypothalamus (anterior)</topic><topic>Hypothalamus (lateral)</topic><topic>Hypothalamus (medial)</topic><topic>Hypothalamus (ventromedial)</topic><topic>Hypothalamus. Hypophysis. Epiphysis. Urophysis</topic><topic>Injection</topic><topic>Intercellular Signaling Peptides and Proteins</topic><topic>Male</topic><topic>Melanin</topic><topic>Melanin-concentrating hormone</topic><topic>Melanins - pharmacology</topic><topic>Microinjections</topic><topic>Neuropeptide Y</topic><topic>Neuropeptide Y - metabolism</topic><topic>Neuropeptides</topic><topic>Neurotransmitters</topic><topic>Nuclei</topic><topic>Paraventricular Hypothalamic Nucleus - drug effects</topic><topic>Paraventricular Hypothalamic Nucleus - metabolism</topic><topic>Paraventricular nucleus</topic><topic>Peptides</topic><topic>Pituitary Hormones - pharmacology</topic><topic>Preoptic area</topic><topic>Preoptic area (medial)</topic><topic>Proteins - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Supraoptic nucleus</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abbott, Caroline R</creatorcontrib><creatorcontrib>Kennedy, Adam R</creatorcontrib><creatorcontrib>Wren, Alison M</creatorcontrib><creatorcontrib>Rossi, Michela</creatorcontrib><creatorcontrib>Murphy, Kevin G</creatorcontrib><creatorcontrib>Seal, Leighton J</creatorcontrib><creatorcontrib>Todd, Jeannie F</creatorcontrib><creatorcontrib>Ghatei, Mohammad A</creatorcontrib><creatorcontrib>Small, Caroline J</creatorcontrib><creatorcontrib>Bloom, Stephen R</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abbott, Caroline R</au><au>Kennedy, Adam R</au><au>Wren, Alison M</au><au>Rossi, Michela</au><au>Murphy, Kevin G</au><au>Seal, Leighton J</au><au>Todd, Jeannie F</au><au>Ghatei, Mohammad A</au><au>Small, Caroline J</au><au>Bloom, Stephen R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of Hypothalamic Nuclei Involved in the Orexigenic Effect of Melanin-Concentrating Hormone</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2003-09-01</date><risdate>2003</risdate><volume>144</volume><issue>9</issue><spage>3943</spage><epage>3949</epage><pages>3943-3949</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract><![CDATA[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 α-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.]]></abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>12933668</pmid><doi>10.1210/en.2003-0149</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Agouti-Related Protein
alpha-MSH - metabolism
Amphetamines
Animals
Appetite - drug effects
Appetite - physiology
Arcuate nucleus
Arcuate Nucleus of Hypothalamus - drug effects
Arcuate Nucleus of Hypothalamus - metabolism
Biological and medical sciences
Cocaine
Cocaine- and amphetamine-regulated transcript protein
Eating - drug effects
Eating - physiology
Explants
Feeding
Feeding Behavior - drug effects
Feeding Behavior - physiology
Fundamental and applied biological sciences. Psychology
Hormones and neuropeptides. Regulation
Hypothalamic Hormones - pharmacology
Hypothalamus
Hypothalamus (anterior)
Hypothalamus (lateral)
Hypothalamus (medial)
Hypothalamus (ventromedial)
Hypothalamus. Hypophysis. Epiphysis. Urophysis
Injection
Intercellular Signaling Peptides and Proteins
Male
Melanin
Melanin-concentrating hormone
Melanins - pharmacology
Microinjections
Neuropeptide Y
Neuropeptide Y - metabolism
Neuropeptides
Neurotransmitters
Nuclei
Paraventricular Hypothalamic Nucleus - drug effects
Paraventricular Hypothalamic Nucleus - metabolism
Paraventricular nucleus
Peptides
Pituitary Hormones - pharmacology
Preoptic area
Preoptic area (medial)
Proteins - metabolism
Rats
Rats, Wistar
Supraoptic nucleus
Vertebrates: endocrinology
title Identification of Hypothalamic Nuclei Involved in the Orexigenic Effect of Melanin-Concentrating Hormone
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