Dopaminergic Neurotransmission in the Nucleus Accumbens Modulates Social Play Behavior in Rats
Open accessAbstract
Social play behavior is a highly rewarding form of social interaction displayed by young mammals. Social play is important for neurobehavioral development and it has been found to be impaired in several developmental psychiatric disorders. In line with the rewarding properties of social play, we have previously identified the nucleus accumbens (NAc) as an important site of action for endocannabinoid and opioid modulation of this behavior. NAc dopamine has a well-known role in certain components of reward processes, such as incentive motivation. However, its contribution to the positive emotional aspects of social interactions is less clear. Therefore, we investigated the role of dopaminergic neurotransmission in the NAc in social play behavior in rats. We found that intra-NAc infusion of the dopamine releaser/reuptake inhibitor amphetamine increased social play behavior that was dependent on activation of both D1 and D2 dopamine receptors. This increase in social play behavior was mimicked by intra-NAc infusion of the dopamine receptor agonist apomorphine, but not of the dopamine reuptake inhibitor GBR-12909. Blockade of either D1 or D2 NAc dopamine receptors reduced social play in animals highly motivated to play as a result of longer social isolation before testing. Last, blockade of NAc dopamine receptors prevented the play-enhancing effects of endocannabinoid and opioid receptor stimulation. These findings demonstrate an important modulatory role of NAc dopaminergic neurotransmission in social play. Thus, functional activity in the mesolimbic dopamine pathway plays an important role in adaptive social development, whereas abnormal NAc dopamine function may underlie the social impairments observed in developmental psychiatric disorders such as autism, attention deficit hyperactivity disorder or early-onset schizophrenia.
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Up to 24 h, longer periods of isolation induce more play in rats.
“Indeed, up to 24 h, longer periods of isolation induce more play (Panksepp and Beatty, 1980), but see Manduca et al. (2016) for an exception.”
From Effects of Maternal Deprivation and Complex Housing on Rat Social Behavior in Adolescence and Adulthood (2018) · cites this paper as Manduca et al., 2016
Manduca et al. is cited as an exception to the claim that longer isolation increases play up to 24 hours. Instead, the paper’s section on pharmacological manipulation of nucleus accumbens dopamine reports that vehicle-treated rats isolated for 24 hours showed about twice as much social play as rats isolated for 2 hours. Our copy provides no page number for this passage. (LLM, conf=0.87)
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Experimental — accuracy not yet measuredLittle is known about the sites of action of dopamine and norepinephrine signaling in the brain involved in social play behavior.
“Despite a few studies using local manipulation of the DA and NE systems [10,11], little is known about the sites of action of DA and NE signaling in the brain involved in social play behavior.”
From Involvement of dopamine, but not norepinephrine, in the sex-specific regulation of juvenile socially rewarding behavior by vasopressin (2018) · cites this paper as [11]
The Introduction (page unavailable) describes uncertainty about where dopamine acts in social play and explains why the authors tested local manipulation in the nucleus accumbens. This supports the dopamine portion of the claim, but the paper does not establish a comparable knowledge gap for norepinephrine. (LLM, conf=0.83)
Experimental — accuracy not yet measuredIn juvenile male rats, administration of a D1 receptor antagonist, a D2 receptor antagonist, or the non-specific DA receptor antagonist alpha-flupenthixol reduces social play behavior.
“administration of a D1 receptor antagonist, a D2 receptor antagonist, or the non-specific DA receptor antagonist alpha-flupenthixol reduced social play behavior in juvenile male rats (females were not tested [11]).”
From Involvement of dopamine, but not norepinephrine, in the sex-specific regulation of juvenile socially rewarding behavior by vasopressin (2018) · cites this paper as [11]
The Discussion reports that intra-NAc α-flupenthixol, the D1 antagonist SCH-23390, and the D2 antagonist eticlopride reduced social play in rats isolated for 24 hours or 7 days before testing. It also says these drugs did not generally reduce social play after brief isolation, a condition the citing sentence omits. The Animals section identifies the rats as male; females were not tested. Page numbers were unavailable in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIntra-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 shell.
“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.”
From Peripubertal stress increases play fighting at adolescence and modulates nucleus accumbens CB1 receptor expression and mitochondrial function in the amygdala (2018) · cites this paper as [56]
The Discussion (page not available in our copy) says pilot infusions of amphetamine into both the NAc core and shell stimulated social play. It also discusses local opioid signaling in those subregions, but does not identify DAMGO or report that DAMGO infusion enhanced play fighting in both. (LLM, conf=0.87)
Experimental — accuracy not yet measuredDA neurotransmission in the nucleus accumbens modulates social play behavior.
“DA neurotransmission in the nucleus accumbens was also found to modulate social play behavior.”
From Involvement of dopamine, but not norepinephrine, in the sex-specific regulation of juvenile socially rewarding behavior by vasopressin (2018) · cites this paper as [11]
Substantial evidence supports the involvement of both NAc shell and core in play fighting.
“Substantial evidence supports the involvement of both NAc shell and core in play fighting.”
Directly stimulating dopaminergic signalling in the nucleus accumbens enhances social play behaviour.
“and directly stimulating dopaminergic signalling in the nucleus accumbens enhances social play behaviour (Manduca et al. 2016).”
From Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia (2025) · cites this paper as Manduca et al. 2016
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“Indeed, dopamine has been implicated in the motivation for social play (Achterberg et al. 2015) and directly stimulating dopaminergic signalling in the nucleus accumbens enhances social play behaviour (Manduca et al. 2016).”
Self-citation
- Authors
- Manduca, A., Servadio, M., Damsteegt, R., Campolongo, P., Vanderschuren, L. J., & Trezza, V.
- Affiliations
- Roma Tre University (IT)
- University Medical Center Utrecht (NL)
- Sapienza University of Rome (IT)
- Utrecht University (NL)
- Corresponding author
- Trezza, Viviana
- Venue
- Neuropsychopharmacology
- Published
- 2016-02-10
- Volume
- 41
- Issue
- 9
- Pages
- 2215-2223
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4946055
- OpenAlex
- W2288610463
- Cited by
- 149
- References
- 10
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 16 · 2023: 15 · 2022: 16 · 2021: 20 · 2020: 12 · 2019: 13 · 2018: 15 · 2017: 10 · 2016: 3
- FWCI
- 7.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Iris (Roma Tre University) (submittedVersion)
- Funders
- European Commission (293589)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- National Institute on Drug Abuse (R01DA022628, DA022628)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- social play, nucleus accumbens, dopamine signaling, dopamine D1 receptor, dopamine D2 receptor, amphetamine, apomorphine, GBR 12909, social isolation, opioid modulation, mesolimbic dopamine system, social development (developmental psychology), autism spectrum disorder, attention deficit hyperactivity disorder, early-onset schizophrenia
- MeSH terms
- Amphetamine, Animals, Apomorphine, Dopamine, Male, Motivation, Synaptic Transmission, Nucleus Accumbens, Piperazines, Social Behavior, Rats, Wistar, Receptors, Dopamine D1, Receptors, Dopamine D2, Dopamine Uptake Inhibitors, Dopamine D2 Receptor Antagonists
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