Selective localization of oxytocin receptors and vasopressin 1a receptors in the human brainstem
Open accessAbstract
Intranasal oxytocin (OT) affects a suite of human social behaviors, including trust, eye contact, and emotion recognition. However, it is unclear where oxytocin receptors (OXTR) and the structurally related vasopressin 1a receptors (AVPR1a) are expressed in the human brain. We have previously described a reliable, pharmacologically informed receptor autoradiography protocol for visualizing these receptors in postmortem primate brain tissue. We used this technique in human brainstem tissue to identify the neural targets of OT and vasopressin. To determine binding selectivity of the OXTR radioligand and AVPR1a radioligand, sections were incubated in four conditions: radioligand alone, radioligand with the selective AVPR1a competitor SR49059, and radioligand with a low or high concentration of the selective OXTR competitor ALS-II-69. We found selective OXTR binding in the spinal trigeminal nucleus, a conserved region of OXTR expression in all primate species investigated to date. We found selective AVPR1a binding in the nucleus prepositus, an area implicated in eye gaze stabilization. The tissue's postmortem interval (PMI) was not correlated with either the specific or nonspecific binding of either radioligand, indicating that it will not likely be a factor in similar postmortem studies. This study provides critical data for future studies of OXTR and AVPR1a in human brain tissue.
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In humans, visual processing of social cues is facilitated by intranasal oxytocin through increased attention to and recognition of emotional cues in faces.
“Similarly, in humans, visual processing of social cues is facilitated by IN-OT through increased attention to and recognition of emotional cues in faces [98,99].”
From The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives (2023) · cites this paper as [98]
The Introduction (page unavailable) says intranasal oxytocin can affect eye contact and emotion recognition in healthy humans, and the References list a study of increased gaze to the eye region of faces. The paper does not establish that increased attention and recognition are the mechanism by which intranasal oxytocin facilitates visual processing; the Introduction says that mechanism remains unclear. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe neuroanatomical map of OXTR binding in the human brain has not been reliably characterized, except for two outdated studies whose results have recently been called into question due to the radioligand's high degree of cross-reactivity to AVPR1a.
“The neuroanatomical map of OXTR binding in the human brain has not been reliably characterized, except for two outdated studies35,36 whose results have recently been called into question34 due to the radioligand’s high degree of cross-reactivity to the structurally similar vasopressin 1a receptor (AVPR1a).”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [34]
The optimized and reliable method for measuring OXTR and AVPR1a has been previously validated in nonhuman primate and human brain tissue to selectively reveal OXTR or AVPR1a.
“we measured both OXTR and AVPR1a with an optimized and reliable method previously validated in nonhuman primate and human brain tissue34,37,38.”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [34]
The absence of a PMI effect suggests that the tertiary structure and pharmacological features of OXTR remain intact across brain regions for extended periods of time after death.
“which supports and extends the results from our previous study in postmortem human brainstem tissue34 and suggests that the tertiary structure and pharmacological features of OXTR remain intact across brain regions for extended periods of time after death.”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [34]
Multiple analyses from human brains with a PMI range of 5-33 h found no association between post-mortem interval and optical binding density for these ligands.
“multiple analyses from human brains with a PMI range of 5–33 h found no association between post-mortem interval and optical binding density for these ligands”
From Distribution of brain oxytocin and vasopressin V1a receptors in chimpanzees (Pan troglodytes): comparison with humans and other primate species (2022) · cites this paper as Freeman et al. 2016
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Self-citation
- Authors
- Freeman, S. M., Smith, A. L., Goodman, M. M., & Bales, K. L.
- Affiliations
- University of California, Davis (US)
- Emory University (US)
- Corresponding author
- Freeman, Sara M.
- Venue
- Social Neuroscience
- Publisher
- Informa UK Limited
- Published
- 2016-03-10
- Volume
- 12
- Issue
- 2
- Pages
- 113-123
- ISSN
- 1747-0919 (ISSN-L)
- 1747-0927
- PMC
- PMC5474119
- OpenAlex
- W2290898970
- Cited by
- 51
- References
- 43
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 9 · 2020: 3 · 2019: 2 · 2018: 14 · 2017: 10 · 2016: 5
- FWCI
- 16.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Social Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (P51OD011107)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Keywords
- oxytocin receptor, vasopressin 1a receptor, human brainstem, receptor autoradiography, spinal trigeminal nucleus, postmortem interval, intranasal oxytocin, social behavior
- MeSH terms
- Acetylcholinesterase, Adolescent, Adult, Autoradiography, Brain Stem, Humans, Male, Middle Aged, Receptors, Vasopressin, Receptors, Oxytocin, Young Adult
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