Oxytocin in the nucleus accumbens shell reverses CRFR2-evoked passive stress-coping after partner loss in monogamous male prairie voles
Open accessAbstract
Loss of a partner can have severe effects on mental health. Here we explore the neural mechanisms underlying increased passive stress-coping, indicative of depressive-like behavior, following the loss of the female partner in the monogamous male prairie vole. We demonstrate that corticotropin-releasing factor receptor 2 (CRFR2) in the nucleus accumbens shell mediates social loss-induced passive coping. Further, we show that partner loss compromises the oxytocin system through multiple mechanisms. Finally, we provide evidence for an interaction of the CRFR2 and oxytocin systems in mediating the emotional consequences of partner loss. Our results suggest that chronic activation of CRFR2 and suppression of striatal oxytocin signaling following partner loss result in an aversive emotional state that may share underlying mechanisms with bereavement. We propose that the suppression of oxytocin signaling is likely adaptive during short separations to encourage reunion with the partner and may have evolved to maintain long-term partnerships. Additionally, therapeutic strategies targeting these systems should be considered for treatment of social loss-mediated depression.
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Activating CRF2s centrally decreases OT release in the NAc, whereas blocking CRF2s elevates OT release in this region.
“Activating CRF2s centrally decreases OT release in the NAc, whereas blocking CRF2s elevates OT release in this region [169].”
From The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives (2023) · cites this paper as [169]
CRF mRNA is elevated in the BNST of pair-bonded male voles compared to non-paired males, and CRF2s colocalize to OT neurons in the PVN and OT fibers projecting to the NAc.
“Interestingly, CRF mRNA is elevated in the BNST of pair-bonded male voles, as compared to non-paired males, and CRF2s colocalize to OT neurons in the PVN and OT fibers projecting to the NAc [166,169].”
From The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives (2023) · cites this paper as [169]
Loss of oxytocin signaling following partner loss also mediates depressive-like behavior reminiscent of grieving.
“Loss of oxytocin signaling following partner loss also mediates depressive-like behavior reminiscent of grieving”
From Oxytocin, Neural Plasticity, and Social Behavior (2021) · cites this paper as Bosch et al. 2016
Blockade of endogenous OTR (and other neuromodulatory receptor) signaling in the NAc inhibits pair bond formation and other forms of social behavior in prairie voles and other rodents.
“blockade of endogenous OTR (and other neuromodulatory receptor) signaling in the NAc inhibits pair bond formation and other forms of social behavior in prairie voles and other rodents”
From Oxytocin receptors modulate a social salience neural network in male prairie voles (2017) · cites this paper as Bosch et al., 2016
Losing the female-bonded partner causes dysregulations of the fine-tuned brain OT system on multiple levels in male prairie voles.
“losing the female-bonded partner causes dysregulations of the fine-tuned brain OT system on multiple levels in male prairie voles”
From Oxytocin and Social Relationships: From Attachment to Bond Disruption (2017) · cites this paper as Bosch et al. 2016
On the fifth day of separation, OT mRNA expression is decreased within the hypothalamic PVN, but not the supraoptic nucleus, compared with non-separated males.
“On the fifth day of separation, OT mRNA expression is decreased within the hypothalamic paraventricular nucleus (PVN), but not the supraoptic nucleus, the two major sources for OT released within the brain, compared with non-separated males”
From Oxytocin and Social Relationships: From Attachment to Bond Disruption (2017) · cites this paper as Bosch et al. 2016
OT signaling to the NAc shell is impaired following loss of the female partner.
“Thus, the data suggest that the OT signaling to the NAc shell is impaired following loss of the female partner.”
From Oxytocin and Social Relationships: From Attachment to Bond Disruption (2017) · cites this paper as Bosch et al. 2016
Chronic infusion of CRF-R2 agonist increases passive stress-coping in non-separated males.
“On the contrary, chronic infusion of CRF-R2 agonist (stresscopin) increases passive stress-coping in non-separated males”
From Oxytocin and Social Relationships: From Attachment to Bond Disruption (2017) · cites this paper as Bosch et al. 2016
Chronic local infusion of OT within the NAc shell normalizes passive stress-coping behavior in separated male prairie voles.
“it is striking that chronic local infusion of OT within the NAc shell normalizes passive stress-coping behavior”
From Oxytocin and Social Relationships: From Attachment to Bond Disruption (2017) · cites this paper as Bosch et al. 2016
Partner loss-induced effects on the OT system in the NAc shell of male prairie voles are mediated via the brain CRF system.
“These partner loss-induced effects on the OT system in the NAc shell of male prairie voles are mediated via the brain CRF system”
From Oxytocin and Social Relationships: From Attachment to Bond Disruption (2017) · cites this paper as Bosch et al. 2016
Within the NAc shell, OTR binding is reduced following separation from the female partner.
“Importantly, within the NAc shell, OTR binding is reduced following separation from the female partner”
From Oxytocin and Social Relationships: From Attachment to Bond Disruption (2017) · cites this paper as Bosch et al. 2016
Chronic inactivation of OTR by a selective antagonist or local knock-down by shRNA increases passive stress-coping in males continuously housed with their female partner.
“within the same brain region chronic inactivation of the OTR by a selective OTR antagonist as well as local knock-down of OTR by shRNA increase passive stress-coping in males that are continuously housed with their female partner”
From Oxytocin and Social Relationships: From Attachment to Bond Disruption (2017) · cites this paper as Bosch et al. 2016
CRF-R2 are abundantly expressed on OT neurons in the PVN and on OT fibers projecting to the NAc shell.
“Importantly, CRF-R2 are abundantly expressed on OT neurons in the PVN as well as on its OT fibers projecting to the NAc shell”
From Oxytocin and Social Relationships: From Attachment to Bond Disruption (2017) · cites this paper as Bosch et al. 2016
Losing the female partner is chronic stress in male prairie voles.
“indicating that losing the female partner is chronic stress”
From Oxytocin and Social Relationships: From Attachment to Bond Disruption (2017) · cites this paper as Bosch et al. 2016
Central infusion of CRF-R2 agonist causes reduced local release of OT within the NAc shell in naïve male prairie voles.
“central infusion of CRF-R2 agonist causes reduced local release of OT within the NAc shell in naïve male prairie voles”
From Oxytocin and Social Relationships: From Attachment to Bond Disruption (2017) · cites this paper as Bosch et al. 2016
Central blockade of CRF-R2 increases OT release within the NAc shell.
“In contrast, central blockade of CRF-R2 increases OT release with the NAc shell”
From Oxytocin and Social Relationships: From Attachment to Bond Disruption (2017) · cites this paper as Bosch et al. 2016
Loss of partner in monogamous prairie voles suppresses OTR signaling.
“Indeed, researchers found recently that the loss of partner in monogamous species prairie voles suppresses OTR signaling and that infusion of OT in the NAcc reverses the adverse emotional response to the loss of a partner (Bosch et al. 2016).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Bosch et al. 2016
Infusion of OT in the NAcc reverses the adverse emotional response to the loss of a partner.
“Indeed, researchers found recently that the loss of partner in monogamous species prairie voles suppresses OTR signaling and that infusion of OT in the NAcc reverses the adverse emotional response to the loss of a partner (Bosch et al. 2016).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Bosch et al. 2016
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References 55 · Cited by 140
- Authors
- Bosch, O. J., Dabrowska, J., Modi, M. E., Johnson, Z. V., Keebaugh, A. C., Barrett, C. E., Ahern, T. H., Guo, J., Grinevich, V., Rainnie, D. G., Neumann, I. D., & Young, L. J.
- Affiliations
- University of Regensburg (DE)
- Rosalind Franklin University of Medicine and Science (US)
- Boston Children's Hospital (US)
- Emory University (US)
- German Cancer Research Center (DE)
- Corresponding author
- Bosch, Oliver J.
- Young, Larry J.
- ORCID
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 64
- Pages
- 66-78
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC4698175
- OpenAlex
- W2174046044
- Cited by
- 140
- References
- 55
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 10 · 2023: 17 · 2022: 13 · 2021: 13 · 2020: 16 · 2019: 8 · 2018: 24 · 2017: 13 · 2016: 13
- FWCI
- 27.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Funders
- Rosalind Franklin University of Medicine and Science
- National Institutes of Health (P51OD011132)
- National Institute of Mental Health (R00MH096746, R01MH096983, P50MH100023, R01MH056538, R01MH077776)
- National Institute of Neurological Disorders and Stroke (P30NS055077, NINDS P30NS055077, T32NS096050)
- 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, nucleus accumbens shell, CRFR2, loss of a partner, social loss, depression-like behavior, Microtus ochrogaster, monogamy, bereavement
- MeSH terms
- Adaptation, Psychological, Animals, Autoradiography, Bacterial Proteins, Corpus Striatum, Corticotropin-Releasing Hormone, Arvicolinae, Death, Female, Luminescent Proteins, Male, Membrane Potentials, Microinjections, Neurons, Nucleus Accumbens, Oxytocin, Pair Bond, Paraventricular Hypothalamic Nucleus, Peptide Fragments, Peptides, Cyclic, Radioimmunoassay, Vasotocin, Receptors, Corticotropin-Releasing Hormone, Receptors, Oxytocin, RNA, Small Interfering, Urocortins, Infusions, Intraventricular
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