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Neuroanatomical evidence for reciprocal regulation of the corticotrophin-releasing factor and oxytocin systems in the hypothalamus and the bed nucleus of the stria terminalis of the rat: Implications for balancing stress and affect
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Activation of corticotrophin releasing factor (CRF) neurons in the paraventricular nucleus of the hypothalamus (PVN) is necessary for establishing the classic endocrine response to stress, while activation of forebrain CRF neurons mediates affective components of the stress response. Previous studies have reported that mRNA for CRF2 receptor (CRFR2) is expressed in the bed nucleus of the stria terminalis (BNST) as well as hypothalamic nuclei, but little is known about the localization and cellular distribution of CRFR2 in these regions. Using immunofluorescence with confocal microscopy, as well as electron microscopy, we demonstrate that in the BNST CRFR2-immunoreactive fibers represent moderate to strong labeling on axons terminals. Dual-immunofluorescence demonstrated that CRFR2-fibers co-localize oxytocin (OT), but not arginine-vasopressin (AVP), and make perisomatic contacts with CRF neurons. Dual-immunofluorescence and single cell RT-PCR demonstrate that in the hypothalamus, CRFR2 immunoreactivity and mRNA are found in OT, but not in CRF or AVP-neurons. Furthermore, CRF neurons of the PVN and BNST express mRNA for the oxytocin receptor, while the majority of OT/CRFR2 neurons in the hypothalamus do not. Finally, using adenoviral-based anterograde tracing of PVN neurons, we show that OT/CRFR2-immunoreactive fibers observed in the BNST originate in the PVN. Our results strongly suggest that CRFR2 located on oxytocinergic neurons and axon terminals might regulate the release of this neuropeptide and hence might be a crucial part of potential feedback loop between the hypothalamic oxytocin system and the forebrain CRF system that could significantly impact affective and social behaviors, in particular during times of stress.
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“OT and CRHR2 fibers present in the BnST originated in the PVN.”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Dabrowska et al., 2011
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“Finally, a subpopulation of parvocellular PVN OT and AVP neurons, along with ERβ and coordinating input from the BnST, is thought to be involved in the stress response (135, 139, 140) supporting the possibility that EDCs may influence the hypothalamic–pituitary–adrenal axis.”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [140]
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“Dabrowska et al. (2011) have shown that not only does the BnST interact with the PVN, but also vice versa, presumably through an OT and CRHR2 mechanism”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Dabrowska et al., 2011
In the citing paper
“The partial dissociation in the effect of OT on defensive responses to predictable and unpredictable shocks can be explained by evidence in rodents that OT facilitates excitatory signaling in a structure that underlies sustained anxiety-like behavior to uncertainty, the BNST,7,8 by directly activating corticotrophin releasing factor neurons.”
From Oxytocin increases anxiety to unpredictable threat (2013) · cites this paper as [7]
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“OT released from the paraventricular nucleus of the hypothalamus facilitates excitatory signaling in the bed nucleus of the stria terminalis (BNST),7,8”
From Oxytocin increases anxiety to unpredictable threat (2013) · cites this paper as [7]
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“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 Dabrowska et al. 2011
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Metadata
- Authors
- Dabrowska, J., Hazra, R., Ahern, T. H., Guo, J.-D., McDonald, A. J., Mascagni, F., Muller, J. F., Young, L. J., & Rainnie, D. G.
- Affiliations
- Emory University (US)
- University of Massachusetts Amherst (US)
- University of South Carolina (US)
- Corresponding author
- Rainnie, Donald G.
- ORCID
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 36
- Issue
- 9
- Pages
- 1312-1326
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC3142325
- OpenAlex
- W2019584232
- Cited by
- 274
- References
- 85
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 15 · 2023: 18 · 2022: 13 · 2021: 22 · 2020: 30 · 2019: 21 · 2018: 32 · 2017: 22 · 2016: 15 · 2015: 20 · 2014: 15 · 2013: 18 · 2012: 6
- FWCI
- 18.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (MH07908, MH-077776, MH64692)
- NSF (IBN-9876754)
- National Primate Research Center (RR-00165)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › 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
- corticotropin-releasing factor, oxytocin, CRF2 receptor, bed nucleus of the stria terminalis, paraventricular nucleus, oxytocin receptor, vasopressin, stress response, affective stress, reciprocal regulation, axon terminals, neuropeptide co-localization, social behavior
- MeSH terms
- Affect, Animals, Arginine Vasopressin, Colchicine, Corticotropin-Releasing Hormone, Homeostasis, Hypothalamus, Injections, Intraventricular, Male, Neuroanatomy, Neurons, Oxytocin, Septal Nuclei, Stress, Psychological, Rats, Sprague-Dawley, Receptors, Corticotropin-Releasing Hormone, Feedback, Physiological, Rats
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