Melanocortin Receptor Agonists Facilitate Oxytocin-Dependent Partner Preference Formation in the Prairie Vole
The central melanocortin (MC) system has been widely studied for its effects on food intake and sexual behavior. However, the MC system, and more specifically the MC4 receptor (MC4R), also interacts with neurochemical systems that regulate socioemotional behaviors, including oxytocin (OT) and dopami...
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| Veröffentlicht in: | Neuropsychopharmacology (New York, N.Y.) N.Y.), 2015-07, Vol.40 (8), p.1856-1865 |
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| creator | Modi, Meera E Inoue, Kiyoshi Barrett, Catherine E Kittelberger, Kara A Smith, Daniel G Landgraf, Rainer Young, Larry J |
| description | The central melanocortin (MC) system has been widely studied for its effects on food intake and sexual behavior. However, the MC system, and more specifically the MC4 receptor (MC4R), also interacts with neurochemical systems that regulate socioemotional behaviors, including oxytocin (OT) and dopamine. In monogamous prairie voles, OT and dopamine interact to promote partner preference formation, a laboratory measure of an enduring social bond between mates. Here we investigated the effects of MC receptor activation on partner preference formation in prairie voles, as well as the interaction between the MC and OT systems during this process. Peripheral administration of the brain penetrant MC3/4R receptor peptide agonist, Melanotan II (MTII), and the highly selective, small-molecule MC4R agonist, Pf-446687, enhanced partner preference formation in the prairie vole, but not in the non-monogamous meadow vole. MTII-induced partner preferences were enduring, as they were present 1 week after drug manipulation. The prosocial effects of MCR agonists may be mediated, in part, through modulation of OT, as coadministration of an OT receptor antagonist prevented MTII-induced partner preferences. MTII also selectively activated hypothalamic OT neurons and potentiated central OT release. As OT has been shown to enhance some aspects of social cognition in humans, our data suggest that the MC4R may be a viable therapeutic target for enhancing social function in psychiatric disorders, including autism spectrum disorders and schizophrenia, potentially through activation of the OT system. |
| doi_str_mv | 10.1038/npp.2015.35 |
| format | Article |
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However, the MC system, and more specifically the MC4 receptor (MC4R), also interacts with neurochemical systems that regulate socioemotional behaviors, including oxytocin (OT) and dopamine. In monogamous prairie voles, OT and dopamine interact to promote partner preference formation, a laboratory measure of an enduring social bond between mates. Here we investigated the effects of MC receptor activation on partner preference formation in prairie voles, as well as the interaction between the MC and OT systems during this process. Peripheral administration of the brain penetrant MC3/4R receptor peptide agonist, Melanotan II (MTII), and the highly selective, small-molecule MC4R agonist, Pf-446687, enhanced partner preference formation in the prairie vole, but not in the non-monogamous meadow vole. MTII-induced partner preferences were enduring, as they were present 1 week after drug manipulation. The prosocial effects of MCR agonists may be mediated, in part, through modulation of OT, as coadministration of an OT receptor antagonist prevented MTII-induced partner preferences. MTII also selectively activated hypothalamic OT neurons and potentiated central OT release. As OT has been shown to enhance some aspects of social cognition in humans, our data suggest that the MC4R may be a viable therapeutic target for enhancing social function in psychiatric disorders, including autism spectrum disorders and schizophrenia, potentially through activation of the OT system.</description><identifier>ISSN: 0893-133X</identifier><identifier>EISSN: 1740-634X</identifier><identifier>DOI: 10.1038/npp.2015.35</identifier><identifier>PMID: 25652247</identifier><identifier>CODEN: NEROEW</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject><![CDATA[alpha-MSH - analogs & derivatives ; alpha-MSH - pharmacology ; Animals ; Arginine Vasopressin - antagonists & inhibitors ; Arginine Vasopressin - metabolism ; Arvicolinae ; Autism ; Brain - drug effects ; Brain - metabolism ; Brain research ; Cognition & reasoning ; Dopamine ; Dose-Response Relationship, Drug ; Early Growth Response Protein 1 - metabolism ; Female ; Hormones ; Male ; Mental disorders ; Microtus ; Monogamy ; Neurosciences ; Original ; Oxytocin - metabolism ; Oxytocin - pharmacology ; Pair Bond ; Peptides ; Peptides, Cyclic - pharmacology ; Piperidines - pharmacology ; Preferences ; Pyrrolidines - pharmacology ; R&D ; Receptors, Melanocortin - agonists ; Receptors, Melanocortin - genetics ; Receptors, Melanocortin - metabolism ; Receptors, Oxytocin - agonists ; Receptors, Oxytocin - genetics ; Receptors, Oxytocin - metabolism ; Research & development ; Rodents ; Schizophrenia ; Sex Characteristics ; Sexual behavior ; Sexual Behavior, Animal - drug effects ; Vasotocin - analogs & derivatives ; Vasotocin - pharmacology]]></subject><ispartof>Neuropsychopharmacology (New York, N.Y.), 2015-07, Vol.40 (8), p.1856-1865</ispartof><rights>Copyright Nature Publishing Group Jul 2015</rights><rights>Copyright © 2015 American College of Neuropsychopharmacology 2015 American College of Neuropsychopharmacology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c508t-d9c70aaf0e78af9114dea6e93058913f73f8a7d7ea28ed84187f91ea069e7233</citedby><cites>FETCH-LOGICAL-c508t-d9c70aaf0e78af9114dea6e93058913f73f8a7d7ea28ed84187f91ea069e7233</cites><orcidid>0000000346378992 ; 0000-0003-4637-8992</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839509/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839509/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25652247$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Modi, Meera E</creatorcontrib><creatorcontrib>Inoue, Kiyoshi</creatorcontrib><creatorcontrib>Barrett, Catherine E</creatorcontrib><creatorcontrib>Kittelberger, Kara A</creatorcontrib><creatorcontrib>Smith, Daniel G</creatorcontrib><creatorcontrib>Landgraf, Rainer</creatorcontrib><creatorcontrib>Young, Larry J</creatorcontrib><title>Melanocortin Receptor Agonists Facilitate Oxytocin-Dependent Partner Preference Formation in the Prairie Vole</title><title>Neuropsychopharmacology (New York, N.Y.)</title><addtitle>Neuropsychopharmacology</addtitle><description>The central melanocortin (MC) system has been widely studied for its effects on food intake and sexual behavior. However, the MC system, and more specifically the MC4 receptor (MC4R), also interacts with neurochemical systems that regulate socioemotional behaviors, including oxytocin (OT) and dopamine. In monogamous prairie voles, OT and dopamine interact to promote partner preference formation, a laboratory measure of an enduring social bond between mates. Here we investigated the effects of MC receptor activation on partner preference formation in prairie voles, as well as the interaction between the MC and OT systems during this process. Peripheral administration of the brain penetrant MC3/4R receptor peptide agonist, Melanotan II (MTII), and the highly selective, small-molecule MC4R agonist, Pf-446687, enhanced partner preference formation in the prairie vole, but not in the non-monogamous meadow vole. MTII-induced partner preferences were enduring, as they were present 1 week after drug manipulation. The prosocial effects of MCR agonists may be mediated, in part, through modulation of OT, as coadministration of an OT receptor antagonist prevented MTII-induced partner preferences. MTII also selectively activated hypothalamic OT neurons and potentiated central OT release. As OT has been shown to enhance some aspects of social cognition in humans, our data suggest that the MC4R may be a viable therapeutic target for enhancing social function in psychiatric disorders, including autism spectrum disorders and schizophrenia, potentially through activation of the OT system.</description><subject>alpha-MSH - analogs & derivatives</subject><subject>alpha-MSH - pharmacology</subject><subject>Animals</subject><subject>Arginine Vasopressin - antagonists & inhibitors</subject><subject>Arginine Vasopressin - metabolism</subject><subject>Arvicolinae</subject><subject>Autism</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Brain research</subject><subject>Cognition & reasoning</subject><subject>Dopamine</subject><subject>Dose-Response Relationship, Drug</subject><subject>Early Growth Response Protein 1 - metabolism</subject><subject>Female</subject><subject>Hormones</subject><subject>Male</subject><subject>Mental disorders</subject><subject>Microtus</subject><subject>Monogamy</subject><subject>Neurosciences</subject><subject>Original</subject><subject>Oxytocin - 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However, the MC system, and more specifically the MC4 receptor (MC4R), also interacts with neurochemical systems that regulate socioemotional behaviors, including oxytocin (OT) and dopamine. In monogamous prairie voles, OT and dopamine interact to promote partner preference formation, a laboratory measure of an enduring social bond between mates. Here we investigated the effects of MC receptor activation on partner preference formation in prairie voles, as well as the interaction between the MC and OT systems during this process. Peripheral administration of the brain penetrant MC3/4R receptor peptide agonist, Melanotan II (MTII), and the highly selective, small-molecule MC4R agonist, Pf-446687, enhanced partner preference formation in the prairie vole, but not in the non-monogamous meadow vole. MTII-induced partner preferences were enduring, as they were present 1 week after drug manipulation. The prosocial effects of MCR agonists may be mediated, in part, through modulation of OT, as coadministration of an OT receptor antagonist prevented MTII-induced partner preferences. MTII also selectively activated hypothalamic OT neurons and potentiated central OT release. As OT has been shown to enhance some aspects of social cognition in humans, our data suggest that the MC4R may be a viable therapeutic target for enhancing social function in psychiatric disorders, including autism spectrum disorders and schizophrenia, potentially through activation of the OT system.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>25652247</pmid><doi>10.1038/npp.2015.35</doi><tpages>10</tpages><orcidid>https://orcid.org/0000000346378992</orcidid><orcidid>https://orcid.org/0000-0003-4637-8992</orcidid><oa>free_for_read</oa></addata></record> |
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| issn | 0893-133X 1740-634X |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SpringerLink Journals - AutoHoldings |
| subjects | alpha-MSH - analogs & derivatives alpha-MSH - pharmacology Animals Arginine Vasopressin - antagonists & inhibitors Arginine Vasopressin - metabolism Arvicolinae Autism Brain - drug effects Brain - metabolism Brain research Cognition & reasoning Dopamine Dose-Response Relationship, Drug Early Growth Response Protein 1 - metabolism Female Hormones Male Mental disorders Microtus Monogamy Neurosciences Original Oxytocin - metabolism Oxytocin - pharmacology Pair Bond Peptides Peptides, Cyclic - pharmacology Piperidines - pharmacology Preferences Pyrrolidines - pharmacology R&D Receptors, Melanocortin - agonists Receptors, Melanocortin - genetics Receptors, Melanocortin - metabolism Receptors, Oxytocin - agonists Receptors, Oxytocin - genetics Receptors, Oxytocin - metabolism Research & development Rodents Schizophrenia Sex Characteristics Sexual behavior Sexual Behavior, Animal - drug effects Vasotocin - analogs & derivatives Vasotocin - pharmacology |
| title | Melanocortin Receptor Agonists Facilitate Oxytocin-Dependent Partner Preference Formation in the Prairie Vole |
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