Melanocortin receptor agonists facilitate oxytocin-dependent partner preference formation in the Prairie Vole
Open accessAbstract
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.
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Melanocortin receptor agonists facilitate OT-dependent partner preferences in prairie voles.
“facilitate OT-dependent partner preferences in prairie voles (35, 37, 39, 40)”
From Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies (2016) · cites this paper as [37]
Melanocortin receptor agonists potentiate central OT release in the brain.
“melanocortin receptor agonists potentiate central OT release in the brain (37, 38)”
From Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies (2016) · cites this paper as [37]
Peripheral MT-II facilitates OT-dependent social bonding in prairie voles.
“Peripheral MT-II administration also facilitates OT-dependent social bonding in prairie voles and eliminates the social behaviour deficits associated with neonatal social isolation in prairie voles (23,103,104).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [103]
Peripheral Melanotan-II activates OT neurones and increases central OT release after a physiological stimulus.
“Melanotan-II, an MC4R agonist, given peripherally, activates OT neurones and potentiates central OT release following a physiological stimulus (103).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [103]
Peripheral MT-II removes social behaviour deficits caused by neonatal social isolation in prairie voles.
“Peripheral MT-II administration also facilitates OT-dependent social bonding in prairie voles and eliminates the social behaviour deficits associated with neonatal social isolation in prairie voles (23,103,104).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [103]
Prairie vole studies suggest that pharmacologically evoking oxytocin using melanocortin agonists may be another strategy for enhancing social functioning.
“Prairie vole studies suggest that pharmacologically evoking OXT using melanocortin agonists may be another strategy for enhancing social functioning (162).”
From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [162]
In voles, pharmacologically-increased oxytocin signaling enhances partner preference.
“in voles, pharmacologically-increased oxytocin signaling enhances partner preference [44].”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [44]
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References 53 · Cited by 82
- Authors
- Modi, M. E., Inoue, K., Barrett, C. E., Kittelberger, K. A., Smith, D. G., Landgraf, R., & Young, L. J.
- Affiliations
- Emory University (US)
- Pfizer (United States) (US)
- Max Planck Institute of Psychiatry (DE)
- Corresponding author
- Modi, Meera E
- Venue
- Neuropsychopharmacology
- Published
- 2015-02-05
- Volume
- 40
- Issue
- 8
- Pages
- 1856-1865
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4839509
- OpenAlex
- W2065429777
- Cited by
- 82
- References
- 53
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 1 · 2022: 5 · 2021: 8 · 2020: 20 · 2019: 3 · 2018: 11 · 2017: 11 · 2016: 6 · 2015: 9 · 2014: 1
- FWCI
- 20.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Autism Speaks (AS7745)
- National Institutes of Health (OD P51 OD011132, P51OD011132)
- National Institute of Mental Health (R01MH096983, P50MH100023, R01MH056538)
- National Institute of Neurological Disorders and Stroke (T32NS096050)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- melanocortin receptor agonist, melanocortin-4 receptor, oxytocin, Microtus ochrogaster, monogamy, social bonding, melanotan II, dopamine, Microtus pennsylvanicus, social behavior, autism spectrum disorder, schizophrenia
- MeSH terms
- alpha-MSH, Animals, Arginine Vasopressin, Brain, Arvicolinae, Dose-Response Relationship, Drug, Female, Male, Oxytocin, Pair Bond, Peptides, Cyclic, Piperidines, Pyrrolidines, Sexual Behavior, Animal, Sex Characteristics, Vasotocin, Receptors, Oxytocin, Receptors, Melanocortin, Early Growth Response Protein 1
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