Oxytocin reduces amygdala activity, increases social interactions, and reduces anxiety-like behavior irrespective of NMDAR antagonism
Open accessAbstract
Standard dopamine therapies for schizophrenia are not efficacious for negative symptoms of the disease, including asociality. This reduced social behavior may be due to glutamatergic dysfunction within the amygdala, leading to increased fear and social anxiety. Several studies have demonstrated the prosocial effects of oxytocin in schizophrenia patients. Therefore, this study evaluates the effect of subchronic oxytocin on EEG activity in amygdala of mice during performance of the three-chamber social choice and open field tests following acute ketamine as a model of glutamatergic dysfunction. Oxytocin did not restore social deficits introduced by ketamine but did significantly increase sociality in comparison to the control group. Ketamine had no effect on time spent in the center during the open field trials, whereas oxytocin increased overall center time across all groups, suggesting a reduction in anxiety. Amygdala activity was consistent across all drug groups during social and nonsocial behavioral trials. However, oxytocin reduced overall amygdala EEG power during the two behavioral tasks. Alternatively, ketamine did not significantly affect EEG power throughout the tasks. Decreased EEG power in the amygdala, as caused by oxytocin, may be related to both reduced anxiety and increased social behaviors. Data suggest that separate prosocial and social anxiety pathways may mediate social preference.
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OXT promotes the release of γ-aminobutyric acid (GABA), which reduces neuronal excitability and produces anxiolytic effects.
“OXT promotes the release of γ-aminobutyric acid (GABA), which reduces neuronal excitability and produces anxiolytic effects (Sobota et al., 2015; Yuki, 2023).”
From Music's context-dependent influence on oxytocin, social bonding, and emotion regulation: a systematic review (2026) · cites this paper as Sobota et al., 2015
The Introduction (page unavailable) says oxytocin receptor binding is thought to mediate GABAergic transmission and that inhibitory mechanisms may attenuate amygdala activity. The Discussion (page unavailable) reports reduced anxiety-like behavior with oxytocin. The paper does not establish that oxytocin promotes GABA release or that reduced neuronal excitability is the demonstrated mechanism of its anxiolytic effect. (LLM, conf=0.88)
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- Authors
- Sobota, R., Mihara, T., Forrest, A., Featherstone, R. E., & Siegel, S. J.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Siegel, Steven J.
- Venue
- Behavioral Neuroscience
- Published
- 2015
- Volume
- 129
- Issue
- 4
- Pages
- 389-398
- ISSN
- 0735-7044 (ISSN-L)
- 1939-0084
- PMC
- PMC4518468
- OpenAlex
- W2406026105
- Cited by
- 80
- References
- 54
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 7 · 2023: 15 · 2022: 5 · 2021: 1 · 2020: 8 · 2019: 9 · 2018: 8 · 2017: 5 · 2016: 7 · 2015: 1
- FWCI
- 11.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioral Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (P50MH096891)
- 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 › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- oxytocin, amygdala, ketamine, glutamatergic dysfunction, social behavior, anxiety-like behavior, social anxiety, negative symptoms of schizophrenia, EEG spectral power, NMDA receptor antagonism, prosocial behavior, social preferences
- MeSH terms
- Amygdala, Animals, Anxiety, Disease Models, Animal, Electroencephalography, Ketamine, Male, Mice, Inbred C57BL, Motor Activity, Oxytocin, Schizophrenia, Social Behavior, Receptors, N-Methyl-D-Aspartate, Excitatory Amino Acid Antagonists, Mice, Brain Waves
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