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Nucleus Accumbens μ-Opioid Receptors Mediate Social Reward
Open accessAbstract
Positive social interactions are essential for emotional well-being and proper behavioral development of young individuals. Here, we studied the neural underpinnings of social reward by investigating the involvement of opioid neurotransmission in the nucleus accumbens (NAc) in social play behavior, a highly rewarding social interaction in adolescent rats. Intra-NAc infusion of morphine (0.05–0.1 μg) increased pinning and pouncing, characteristic elements of social play behavior in rats, and blockade of NAc opioid receptors with naloxone (0.5 μg) prevented the play-enhancing effects of systemic morphine (1 mg/kg, s.c.) administration. Thus, stimulation of opioid receptors in the NAc was necessary and sufficient for morphine to increase social play. Intra-NAc treatment with the selective μ-opioid receptor agonist [ d -Ala 2 , N -MePhe 4 ,Gly 5 -ol]enkephalin (DAMGO) (0.1–10 ng) and the μ-opioid receptor antagonist Cys-Tyr- d -Trp-Arg-Thr-Pen-Thr-NH 2 (CTAP) (0.3–3 μg) increased and decreased social play, respectively. The δ-opioid receptor agonist DPDPE ([ d -Pen 2 , d -Pen 5 ]-enkephalin) (0.3–3 μg) had no effects, whereas the κ-opioid receptor agonist U69593 ( N -methyl-2-phenyl- N -[(5 R ,7 S ,8 S )-7-(pyrrolidin-1-yl)-1-oxaspiro[4.5]dec-8-yl]acetamide) (0.01–1 μg) decreased social play. Intra-NAc treatment with β-endorphin (0.01–1 μg) increased social play, but met-enkephalin (0.1–5 μg) and the enkephalinase inhibitor thiorphan (0.1–1 μg) were ineffective. DAMGO (0.1–10 ng) increased social play after infusion into both the shell and core subregions of the NAc. Last, intra-NAc infusion of CTAP (3 μg) prevented the development of social play-induced conditioned place preference. These findings identify NAc μ-opioid receptor stimulation as an important neural mechanism for the attribution of positive value to social interactions in adolescent rats. Altered NAc μ-opioid receptor function may underlie social impairments in psychiatric disorders such as autism, schizophrenia, or personality disorders.
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“Furthermore, intra-NAc infusion of the mu-opioid receptor agonist DAMGO or amphetamine leads to enhanced play fighting when injected either into the core or into the shell19,56.”
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“Substantial evidence supports the involvement of both NAc shell and core in play fighting.”
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Metadata
- Authors
- Trezza, V., Damsteegt, R., Achterberg, E. J. M., & Vanderschuren, L. J. M. J.
- Affiliations
- Roma Tre University (IT)
- University Medical Center Utrecht (NL)
- Utrecht University (NL)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-04-27
- Volume
- 31
- Issue
- 17
- Pages
- 6362-6370
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3098965
- OpenAlex
- W2161751456
- Cited by
- 263
- References
- 76
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 15 · 2023: 15 · 2022: 22 · 2021: 15 · 2020: 21 · 2019: 15 · 2018: 22 · 2017: 12 · 2016: 24 · 2015: 19 · 2014: 14 · 2013: 26 · 2012: 12
- FWCI
- 7.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Iris (Roma Tre University) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- Top Institute Pharma (T5-107)
- National Institute on Drug Abuse (R01DA022628)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Keywords
- nucleus accumbens, mu-opioid receptor, social reward, social play, morphine, DAMGO, CTAP, beta-endorphin, adolescent rats, conditioned place preference, opioid receptor subtypes, social behavior development, thiorphan, enkephalinase inhibition, naloxone
- MeSH terms
- Analgesics, Opioid, Analysis of Variance, Animals, Behavior, Animal, beta-Endorphin, Conditioning, Operant, Dose-Response Relationship, Drug, Male, Motor Activity, Narcotic Antagonists, Nucleus Accumbens, Reward, Social Behavior, Rats, Sprague-Dawley, Receptors, Opioid, mu, Neurotransmitter Agents, Rats
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