Oxytocin activation of neurons in ventral tegmental area and interfascicular nucleus of mouse midbrain
Abstract
Oxytocin (OT) was reported to affect cognitive and emotional behavior by action in ventral tegmental area (VTA) and other brain areas. However, it is still unclear how OT activates VTA and related midline nucleus. Here, using patch-clamp recording, we studied the effects of OT on neuron activity in VTA and interfascicular nucleus (IF). OT dose-dependently and selectively excited small neurons located in medial VTA and the majority of IF neurons but not large neurons in lateral VTA. We found the hyperpolarization-activated current (I(h)) and the membrane capacitance of OT-sensitive neuron were significantly smaller than those of OT-insensitive neurons. The action potential width of OT-sensitive neurons was about half that of OT-insensitive neurons. The OT effect was blocked by the OT receptor antagonist atosiban and WAY-267464 but not by tetrodotoxin, suggesting a direct postsynaptic activation of OT receptors. In addition, the phospholipase C (PLC) inhibitor U73122 antagonized the depolarization by OT. Both the nonselective cation channel (NSCC) antagonist SKF96365 and the Na(+)-Ca(2+) exchanger (NCX) blocker SN-6 attenuated OT effects. These results suggested that the PLC signaling pathway coupling to NSCC and NCX contributes to the OT-mediated activation of neurons in medial VTA and IF. Taken together, our results indicate OT directly acted on medial VTA and especially IF neurons to activate NSCC and NCX via PLC. The direct activation by OT of midbrain neurons may be one mechanism underlying OT effects on social behavior.
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Oxytocin in the VTA activates oxytocin receptors on dopamine neurons and regulates their activity, suggesting that oxytocin in the VTA gates social reward.
“Oxytocin in the VTA activates oxytocin receptors on DA neurons regulates their activity, suggesting that oxytocin in the VTA gates social reward (Hung et al., 2017; Tang et al., 2014; Xiao et al., 2017).”
From Oxytocin neurons mediate the effect of social isolation via the VTA circuits (2022) · cites this paper as Tang et al., 2014
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Oxytocin as a modulator of adaptive behavior: integrating ingestive and social mechanisms
Moseley, P. E., Hammock, E. A. D., & Williams, D. L. (2025) · Physiology & Behavior · doi:10.1016/j.physbeh.2025.114992 · Cited by 1 · see citing works
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0001 · Cited by 1 · see citing works
Central Neural Circuits Regulating Maternal Behavior in Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0005 · Cited by 1 · see citing works
Alloparental Behavior and Paternal Behavior in Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0007 · Cited by 1 · see citing works
Evolutionary Perspectives on the Parental Brain
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0011
Anxiety Reduction and Maternal Aggression in Postpartum Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0006
Development of the Parental Brain in Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0009
Development of the Parental Brain in Humans
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0010
Brain Mechanisms Regulating Maternal Behavior in Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0004
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.002.0006
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.002.0003
Abbreviations Used for Major Brain Regions
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.002.0007
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.002.0004
Zhao, X., Chae, Y. C., Smith, D., Chen, V., DeFelipe, D., Sokol, J. W., Sadangi, A., & Tschida, K. (2025) · eLife · doi:10.7554/elife.94924.2
Pérez-Gozalbo, C., Sanahuja-Irene, S., Martínez‐Garciá, F., & Sánchez-Catalán, M. J. (2026) · Neuropharmacology · doi:10.1016/j.neuropharm.2026.111147
- Authors
- Tang, Y., Chen, Z., Tao, H., Li, C., Zhang, X., Tang, A., & Liu, Y.
- Affiliations
- Central South University (CN)
- Hunan University of Traditional Chinese Medicine (CN)
- Corresponding author
- Liu, Yong
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 77
- Pages
- 277-284
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2018899064
- Cited by
- 68
- References
- 54
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 22 · 2019: 4 · 2018: 6 · 2017: 3 · 2016: 6 · 2015: 4 · 2014: 1
- FWCI
- 5.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81171268)
- 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 › Neuroscience and Neuropharmacology Research
- Keywords
- oxytocin, ventral tegmental area, midbrain neurons, hyperpolarization-activated current, membrane capacitance, oxytocin receptor, phospholipase C signaling, non-selective cation channels, Na+/Ca2+ exchanger, social behavior, neuronal excitability
- MeSH terms
- Action Potentials, Animals, Benzodiazepines, Dose-Response Relationship, Drug, Mesencephalon, Neurons, Oxytocin, Pyrazoles, Vasotocin, Signal Transduction, Ventral Tegmental Area, Patch-Clamp Techniques, Mice
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