Hippocampal microinfusion of oxytocin attenuates the behavioural response to stress by means of dynamic interplay with the glucocorticoid-catecholamine responses
Abstract
The neurohypophysial hormone oxytocin acts as a central nervous system neurotransmitter/neuromodulator. We evaluated the effects of oxytocin on behavioural responses to stress, as well as associated biophysiological responses, in a controlled, prospective animal model. The long‐term effects of exogenous oxytocin microinjected to the hippocampus of male rats were assessed. Animals were exposed to predator scent stress and treated 1 h or 7 days later with oxytocin or vehicle. Behaviours were assessed with the elevated plus‐maze and acoustic startle response tests, 7 days after microinjection and freezing behaviour upon exposure to a trauma‐related cue on day 8. These data served for classification into behavioural response groups. Trauma cue response, circulating corticosterone and oxytocin, hippocampal expression of glucocorticoid and mineralocorticoid receptors, and oxytocin receptor mRNA levels were assessed. The interplay between oxytocin, corticosterone and norepinephrine was assessed. Microinfusion of oxytocin both immediately after predator scent stress exposure or 7 days later, after exposure to trauma cue significantly reduced the prevalence rates of extreme responders and reduced trauma cue freezing responses. Post‐exposure treatment with oxytocin significantly corrected the corticosterone stress response, decreased glucocorticoid receptor expression and increased mineralocorticoid receptor expression in the hippocampus compared to vehicle treatment. High‐dose corticosterone administration together with norepinephrine caused release of plasma oxytocin and hippocampal oxytocin receptor. Oxytocin is actively involved in the neurobiological response to predator scent stress processes and thus warrants further study as a potential therapeutic avenue for the treatment of anxiety‐related disorders.
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In rats, central oxytocin administration either immediately or 7 days after a severe stressor reduced PTSD-like behavior 1 week later.
“In rats, central oxytocin administration either immediately or 7 days after a severe stressor reduced PTSD-like behavior (freezing behavior, acoustic startle response, time spent in enclosed arms of elevated plus maze) 1 week later (26).”
From Intranasal Oxytocin to Prevent Posttraumatic Stress Disorder Symptoms: A Randomized Controlled Trial in Emergency Department Patients (2017) · cites this paper as [26]
In rats, a single central oxytocin administration either immediately or 7 days after a severe stressor was associated with reduced PTSD-like behavior 1 week after administration in comparison to placebo.
“In rats, a single central oxytocin administration either immediately or 7 days after a severe stressor was associated with reduced PTSD-like behavior 1 week after administration in comparison to placebo [53].”
From Efficacy of oxytocin administration early after psychotrauma in preventing the development of PTSD: study protocol of a randomized controlled trial (2014) · cites this paper as [53]
The finding that timing of oxytocin administration matters is not supported by the study of Cohen et al., where both treatment times showed a similar decrease in PTSD-like behavior.
“However, this finding is not supported by the study of Cohen et al. [53], where both treatment times (i.e. immediately after severe stress exposure or 7 days later) showed a similar decrease in PTSD-like behavior.”
From Efficacy of oxytocin administration early after psychotrauma in preventing the development of PTSD: study protocol of a randomized controlled trial (2014) · cites this paper as [53]
Preclinical studies differ in whether the timing of oxytocin intervention in relation to severe stress exposure does not influence the outcome or determines whether the intervention results in beneficial or adverse effects.
“As discussed above, preclinical studies differ in whether the timing of the oxytocin intervention in relation to severe stress exposure either does not influence the outcome [53] or determines whether the intervention results in beneficial or adverse effects [54].”
From Efficacy of oxytocin administration early after psychotrauma in preventing the development of PTSD: study protocol of a randomized controlled trial (2014) · cites this paper as [53]
Administration of oxytocin exerts antidepressant-like effect in rodents.
“Moreover, the administration of oxytocin exerts an antidepressant-like effect in rodents [374-377]”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [374]
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- Authors
- Cohen, H., Kaplan, Z., Kozlovsky, N., Gidron, Y., Matar, M. A., & Zohar, J.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Brunel University of London (GB)
- Tel Aviv University (IL)
- Corresponding author
- Cohen, H.
- Venue
- Journal of Neuroendocrinology
- Publisher
- Wiley
- Published
- 2010-07-16
- Volume
- 22
- Issue
- 8
- Pages
- 889-904
- ISSN
- 0953-8194 (ISSN-L)
- 1365-2826
- OpenAlex
- W2128650352
- Semantic Scholar
- 33d845de8878f6057f90bfd762bd8cc27a938800
- Cited by
- 94
- References
- 78
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 7 · 2022: 5 · 2021: 4 · 2020: 2 · 2019: 10 · 2018: 7 · 2017: 10 · 2016: 8 · 2015: 11 · 2014: 8 · 2013: 5 · 2012: 7
- FWCI
- 7.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, hippocampus, stress response, corticosterone, glucocorticoid receptor, mineralocorticoid receptor, norepinephrine, oxytocin receptor, anxiety-related disorders, neurohypophyseal hormones
- MeSH terms
- Animals, Behavior, Animal, Catecholamines, Corticosterone, Glucocorticoids, Hippocampus, Male, Microinjections, Neuropsychological Tests, Oxytocics, Oxytocin, Receptors, Glucocorticoid, Reflex, Startle, Stress Disorders, Post-Traumatic, Stress, Psychological, Rats, Sprague-Dawley, Receptors, Oxytocin, Receptors, Mineralocorticoid, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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