μ-Opioid receptors within subregions of the striatum mediate pair bond formation through parallel yet distinct reward mechanisms
Open accessAbstract
The prairie vole is a socially monogamous rodent that is an excellent animal model for studies of the neurobiology of social attachment. Such studies have demonstrated that activation of reward circuitry during social interactions facilitates pair bond formation. Within this circuitry, μ-opioid receptors (MORs) modulate naturally rewarding behavior in an anatomically segregated manner; MORs located throughout the striatum (dorsal striatum, NAc core, and the entire NAc shell) are implicated in general motivational processes, whereas those located specifically within the dorsomedial NAc shell mediate positive hedonics (and are referred to as a "hedonic hotspot"). The purpose of the present study was to determine whether MORs within these distinct subregions differentially mediate pair bond formation. We first used receptor autoradiography to compare MOR binding densities between these regions. MOR binding was significantly higher in the NAc core and dorsomedial NAc shell compared with the ventral NAc shell. We next used partner preference testing to determine whether MORs within these subregions differentially mediate pair bonding. Blockade of MORs using 1 or 3 μg of H-d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 within the dorsal striatum decreased mating during the cohabitation period and inhibited partner preference formation. In contrast, blockade of MORs within dorsomedial NAc shell inhibited partner preference formation without effecting mating behavior, whereas other regions were not involved. Thus, MORs within the dorsal striatum mediate partner preference formation via impairment of mating, whereas those in the dorsomedial NAc shell appear to mediate pair bond formation through the positive hedonics associated with mating.
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μ-opioid receptors have been studied in relation to reward, emotion, and behavior in the social domain and are strongly expressed in reward-related regions of the primate brain.
“μ-opioid receptors have been studied in relation to reward, emotion, and behavior in the social domain (12) and are strongly expressed in reward-related regions of the primate brain (13).”
From Oxytocin under opioid antagonism leads to supralinear enhancement of social attention (2017) · cites this paper as [12]
Prior to this study, dopamine function had never been studied in relation to social interaction beyond the dyad; past research showed links only to romantic relationships or parenting.
“To our knowledge, dopamine function has never before been studied in relation to social interaction beyond the dyad, with past research showing links only to romantic relationships or parenting (15, 39, 40).”
From Variation in the β-endorphin, oxytocin, and dopamine receptor genes is associated with different dimensions of human sociality (2017) · cites this paper as [15]
Both the dopamine and opioid systems have been shown to interact to maintain monogamous pair bonds in prairie voles.
“For instance, both the dopamine and opioid systems have been shown to interact to maintain monogamous pair bonds in prairie voles (15, 38).”
From Variation in the β-endorphin, oxytocin, and dopamine receptor genes is associated with different dimensions of human sociality (2017) · cites this paper as [15]
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- Authors
- Resendez, S. L., Dome, M., Gormley, G., Franco, D., Nevárez, N., Hamid, A. A., & Aragona, B. J.
- Affiliations
- University of Michigan (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-05-22
- Volume
- 33
- Issue
- 21
- Pages
- 9140-9149
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6705037
- OpenAlex
- W2032055424
- Cited by
- 93
- References
- 100
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 9 · 2020: 5 · 2019: 3 · 2018: 6 · 2017: 19 · 2016: 10 · 2015: 8 · 2014: 9 · 2013: 2
- FWCI
- 14.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (0953106)
- 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 › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- mu-opioid receptor, pair bonding, Microtus ochrogaster, social attachment, reward systems, dorsal striatum, nucleus accumbens shell, nucleus accumbens core, mate preferences, mating behavior, opioid receptor blockade, social monogamy
- MeSH terms
- Animals, Corpus Striatum, Arvicolinae, Dose-Response Relationship, Drug, Female, Male, Motor Activity, Narcotic Antagonists, Nucleus Accumbens, Pair Bond, Peptides, Protein Binding, Reward, Receptors, Opioid, mu
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