Oxytocin Exerts Antidepressant-like effect by potentiating dopaminergic synaptic transmission in the mPFC
Abstract
Oxytocin (OT) and dopamine (DA) are two important elements that are closely related to mental and reward processes in the brain. OT controlled DA functional regulation contributes to various behaviours such as social reward, social cognition and emotion-related behaviours. Previous studies indicated that diminished dopaminergic transmission in the medial prefrontal cortex (mPFC) is correlated with the pathophysiology of depression. However, the interaction of OT and DA and their roles in antidepressant effects still require further exploration. Here, we investigated the antidepressant effect of OT through local mPFC administration, and further explored the underlying mechanisms that indicated that OT could strengthen dopaminergic synaptic transmission with OT receptor (OTR) activation dependent in the mPFC. Our results showed that local administration of OT in the mPFC exerts antidepressant (-like) effects in both naïve and social defeat stress (SDS) depressive animal model. Mechanism study suggested that OT enhances DA level with OTR activation dependent, and elevated mPFC DA levels might further enhance excitatory synaptic transmission by activating the D1/PKA/DARPP32 intracellular signalling pathway in the mPFC. Hence, our study revealed that the activation of OTR strengthens excitatory synaptic transmission via the potentiation of dopaminergic synaptic transmission, especially via D1R activation dependent, in the mPFC, which may be the underlying mechanism of antidepressant (-like) effects mediated by OT. With specifically activation of the D1/PKA/DAPRR32 signalling pathway, our results may augment the important role of OT in reward circuits in the central nervous system.
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Acute stress may promote social interactions at least in part via upregulation of DA input activity in the mPFC, whereas chronic stressors appear to lead to a hypodopaminergic state.
“Thus, acute stress may promote social interactions at least in part via upregulation of DA input activity in the mPFC [155], whereas chronic stressors appear to lead to a hypodopaminergic state [162].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [162]
Infusion of OXT into the mPFC following CSDS had antidepressant actions, associated with increased DA levels and enhanced excitatory synaptic transmission in the mPFC.
“infusion of OXT into the mPFC following CSDS had antidepressant actions, which were associated with increased DA levels, as well as enhanced excitatory synaptic transmission, in the mPFC [162].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [162]
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- Authors
- Li, Q., Zhang, B., Cao, H., Liu, W., Guo, F., Shen, F., Ye, B., Liu, H., Li, Y., & Liu, Z.
- Affiliations
- Tongji University (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Zhang, Bing
- Li, Yang
- Liu, Zhiqiang
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 162
- Pages
- 107836
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2989512761
- Semantic Scholar
- bce5522e0ba9777e1b28a2ba357996970ce39e72
- Cited by
- 47
- References
- 78
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 9 · 2023: 2 · 2022: 4 · 2021: 10 · 2020: 7
- FWCI
- 6.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81771188, 31671049, 81901376)
- Ministry of Science and Technology of the People’s Republic of China (2013CB91060101)
- China Postdoctoral Science Foundation (2017M621535)
- Fundamental Research Funds for the Central Universities (22120180534)
- Shanghai Municipal Commission of Health and Family Planning (201740072)
- Science and Technology Commission of Shanghai Municipality (14411966700, 16411967400)
- Pudong New Area Municipal Commission of Health and Family Planning (PW2016D-10)
- Chinese Academy of Sciences (XDA12040302, XDA12040214)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- oxytocin, antidepressant-like effects, dopamine, medial prefrontal cortex, oxytocin receptor, social defeat stress, depression, excitatory synaptic transmission, dopamine D1 receptor, reward systems
- MeSH terms
- Open Field Test, Social Defeat, Animals, Antidepressive Agents, Behavior, Animal, Depression, Disease Models, Animal, Dopamine, Male, Synaptic Transmission, Oxytocin, Stress, Psychological, Signal Transduction, Prefrontal Cortex, Receptors, Dopamine D1, Cyclic AMP-Dependent Protein Kinases, Pyramidal Cells, Receptors, Oxytocin, Excitatory Postsynaptic Potentials, Mice, Dopamine and cAMP-Regulated Phosphoprotein 32
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