Localization of oxytocin binding sites in the human brainstem and upper spinal cord: an autoradiographic study
Abstract
Two different ligands, tritiated oxytocin and a newly synthesized and monoiodinated oxytocin antagonist, were used to reveal sites which bind oxytocin in the brainstem and upper spinal cord of 12 human subjects. Tissue sections were incubated with either ligand at a concentration close to their respective dissociation constants determined in human uterus and rat brain. Specificity of binding was assessed in presence of unlabelled oxytocin in excess. Comparable results were obtained using tritiated or iodinated ligand. Labelling was most intense in the substantia nigra pars compacta, the substantiae gelatinosae of the caudal spinal trigeminal nucleus and of the dorsal horn of the upper spinal cord, as well as in the medio-dorsal region of the nucleus of the solitary tract. Binding was also detected in the rest of the nucleus of the solitary tract and in other areas, including the oral and interpolar parts of the spinal trigeminal nucleus, the hypoglossal nucleus and the area postrema. Presence of oxytocin binding sites in regions concerned with sensory, autonomic and motor processing suggests that oxytocin could act as a neurotransmitter or neuromodulator in the human central nervous system.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The vagus is densely populated with oxytocin receptors in rodents.
“The vagus is densely populated with oxytocin receptors in rodents19,21–26”
From Voluntary upregulation of heart rate variability through biofeedback is improved by mental contemplative training (2019) · cites this paper as [25]
The vagus nerve is densely populated by oxytocin receptors.
“The vagus nerve is densely populated by oxytocin receptors19,21–26”
From Voluntary upregulation of heart rate variability through biofeedback is improved by mental contemplative training (2019) · cites this paper as [25]
The neuroanatomical map of OXTR binding in the human brain has not been reliably characterized, except for two outdated studies whose results have recently been called into question due to the radioligand's high degree of cross-reactivity to AVPR1a.
“The neuroanatomical map of OXTR binding in the human brain has not been reliably characterized, except for two outdated studies35,36 whose results have recently been called into question34 due to the radioligand’s high degree of cross-reactivity to the structurally similar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 [36]
Before the pharmacological limitations were understood, these radioligands were used for receptor autoradiography in the common marmoset, rhesus macaque, and human.
“Nevertheless, before these pharmacological limitations were fully understood, these radioligands (as well as the older tritiated versions of the endogenous neuropeptides themselves) were used for receptor autoradiography in three primate species: in the common marmoset for OXTR and AVPR1a (29,30), in the rhesus macaque for AVPR1a (31), and in human for OXTR and AVPR1a (32,33).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [33]
Loup et al. (1989; 1991) did not use a competitive binding strategy.
“Loup. et al. (1989; 1991) did not use a competitive binding strategy”
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 Loup et al. 1989
Cites
The rat brain in stereotaxic coordinates
Palkovits, M. (1983) · Neuropeptides · doi:10.1016/0143-4179(83)90049-5 · Cited by 28,959 · see citing works
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
Handbook of Chemical Neuroanatomy
Stern, C. D. (1986) · Neurochemistry International · doi:10.1016/0197-0186(86)90021-5 · Cited by 4,159 · see citing works
The Human Central Nervous System
Nieuwenhuys, R., Voogd, J., & van Huijzen, C. (2008) · doi:10.1007/978-3-540-34686-9 · Cited by 1,262 · see citing works
Cytoarchitecture of the Human Brain Stem.
Boyd, J. D. (1955) · Archives of Ophthalmology · doi:10.1001/archopht.1955.00930010774037 · Cited by 897 · see citing works
Oxytocin receptors in the human uterus during pregnancy and parturition
Fuchs, A., Fuchs, F., Husslein, P. W., & Soloff, M. S. (1984) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(84)90677-x · Cited by 612 · see citing works
Herkenham, M. (1987) · Neuroscience · doi:10.1016/0306-4522(87)90268-5 · Cited by 520 · see citing works
Tribollet, E., Barberis, C., Jard, S., Dubois-Dauphin, M., & Dreifuss, J. J. (1988) · Brain Research · doi:10.1016/0006-8993(88)91437-0 · Cited by 442 · see citing works
Self-citationCytoarchitecture of the Human Brain Stem
(1955) · JAMA · doi:10.1001/jama.1955.02950190099043 · Cited by 417 · see citing works
Sofroniew, M. V. (1980) · Journal of Histochemistry & Cytochemistry · doi:10.1177/28.5.7381192 · Cited by 317 · see citing works
125I-labelled d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH29]OVT: a selective oxytocin receptor ligand
Elands, J., Barberis, C., Jard, S., Tribollet, E., Dreifuss, J.-J., Bankowski, K., Manning, M., & Sawyer, W. H. (1988) · European Journal of Pharmacology · doi:10.1016/0014-2999(88)90778-9 · Cited by 245 · see citing works
Self-citationTribollet, E., Charpak, S., Schmidt, A., Dubois-Dauphin, M., & Dreifuss, J. (1989) · The Journal of Neuroscience · doi:10.1523/jneurosci.09-05-01764.1989 · Cited by 228 · see citing works
Self-citationFreund-Mercier, M. J., Stoeckel, M. E., Palacios, J. M., Pazos, A., Reichhart, J. M., Porte, A., & Richard, P. (1987) · Neuroscience · doi:10.1016/0306-4522(87)90113-8 · Cited by 192 · see citing works
Vasopressin and oxytocin—their role in neurotransmission
Buijs, R. M. (1983) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(83)90056-6 · Cited by 189 · see citing works
Topography of binding sites for neurohypophyseal hormones in rat brain
de Kloet, E. R., Rotteveel, F. T. M., Voorhuis, T. A. M., & Terlou, M. (1985) · European Journal of Pharmacology · doi:10.1016/0014-2999(85)90036-6 · Cited by 161 · see citing works
Audigier, S., & Barberis, C. (1985) · The EMBO Journal · doi:10.1002/j.1460-2075.1985.tb03794.x · Cited by 156 · see citing works
The Human Central Nervous System
Nieuwenhuys, R., Voogd, J., & van Huijzen, C. (1981) · Springer eBooks · doi:10.1007/978-3-662-02333-4 · Cited by 129 · see citing works
Vasopressin, oxytocin and neurophysins in the human brain and spinal cord
Jenkins, J. S., Ang, V. T. Y., Hawthorn, J., Rossor, M. N., & Iversen, L. L. (1984) · Brain Research · doi:10.1016/0006-8993(84)90656-5 · Cited by 126 · see citing works
The mismatch problem in receptor mapping studies
Kuhar, M. J. (1985) · Trends in Neurosciences · doi:10.1016/0166-2236(85)90076-1 · Cited by 119 · see citing works
(1981) · PubMed · Cited by 117 · see citing works
Characterization of a uterine-type oxytocin receptor in the rat hippocampus.
Mühlethaler, M., Sawyer, W. H., Manning, M., & Dreifuss, J. J. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.21.6713 · Cited by 106 · see citing works
Self-citationSolid-phase synthesis of 16 potent (selective and nonselective) in vivo antagonists of oxytocin
Manning, M., Kruszynski, M., Bańkowski, K., Olma, A., Lammek, B., Cheng, L., Kliś, W. A., Seto, J., Haldar, J., & Sawyer, W. H. (1989) · Journal of Medicinal Chemistry · doi:10.1021/jm00122a016 · Cited by 106 · see citing works
Neurotransmitter actions in the vertebrate nervous system
COYLE, J. T. (1986) · Cell · doi:10.1016/0092-8674(86)90551-9 · Cited by 103 · see citing works
Neurotransmitter actions in the vertebrate nervous system
(1987) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(87)90190-x · Cited by 100 · see citing works
van Leeuwen, F. W., van Heerikhuize, J. J., van der Meulen, G., & Wolters, P. S. (1985) · Brain Research · doi:10.1016/0006-8993(85)91443-x · Cited by 95 · see citing works
Schoenen, J. E., Lotstra, F., Vierendeels, G., Reznik, M., & Vanderhaeghen, J. J. (1985) · Neurology · doi:10.1212/wnl.35.6.881 · Cited by 90 · see citing works
[3H]-[Thr4,Gly7]OT: a highly selective ligand for central and peripheral OT receptors
Elands, J., Barberis, C., & Jard, S. (1988) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1988.254.1.e31 · Cited by 88 · see citing works
Raggenbass, M., Dubois‐Dauphin, M., Charpak, S., & Dreifuss, J. J. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.11.3926 · Cited by 79 · see citing works
Self-citationDreifuss, J. J., Raggenbass, M., Charpak, S., Dubois‐Dauphin, M., & Tribollet, E. (1988) · Brain Research Bulletin · doi:10.1016/0361-9230(88)90089-5 · Cited by 76 · see citing works
Self-citationOxytocin in Alzheimer's disease
Mazurek, M. F., Beal, M. F., Bird, E. D., & Martin, J. B. (1987) · Neurology · doi:10.1212/wnl.37.6.1001 · Cited by 70 · see citing works
Oxytocin Receptors in Nonpregnant Human Uterus
Fuchs, A., Fuchs, F., & Soloff, M. S. (1985) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-60-1-37 · Cited by 62 · see citing works
Manzini, S., Hoyle, C. H. V., & Burnstock, G. (1986) · European Journal of Pharmacology · doi:10.1016/0014-2999(86)90364-x · Cited by 61 · see citing works
Raggenbass, M., Tribollet, E., Dubois‐Dauphin, M., & Dreifuss, J. J. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.2.750 · Cited by 59 · see citing works
Self-citationOxytocin and Vasopressin: Distinct Receptors in Myometrium
Guillon, G., Balestre, M., Roberts, J. M., & Bottari, S. P. (1987) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-64-6-1129 · Cited by 56 · see citing works
Neurosecretion: Cellular Aspects Of The Production And Release Of Neuropeptides
Pickering, B. T., Wakerley, J. B., & Summerlee, A. J. S. (2012) · Medical Entomology and Zoology · Cited by 30 · see citing works
Parkinson's disease: Nigral receptor changes support peptidergic role in nigrostriatal modulation
Uhl, G. R., Hackney, G. O., Torchia, M., et al. (1986) · Annals of Neurology · doi:10.1002/ana.410200204 · Cited by 27 · see citing works
Mühlethaler, M., Raggenbass, M., & Dreifuss, J.-J. (1985) · Springer eBooks · doi:10.1007/978-1-4684-4961-7_15 · Cited by 19 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The oxytocin receptor system: structure, function, and regulation
Gimpl, G., & Fahrenholz, F. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.629 · Cited by 3,089 · see citing works
Pathophysiology of Sleep Apnea
Dempsey, J. A., Veasey, S. C., Morgan, B. J., & O'Donnell, C. P. (2010) · Physiological Reviews · doi:10.1152/physrev.00043.2008 · Cited by 2,243 · see citing works
The Social Salience Hypothesis of Oxytocin
Shamay-Tsoory, S. G., & Abu-Akel, A. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.07.020 · Cited by 904 · see citing works
“In humans, OT has a myriad of binding sites across the brain, including limbic and autonomic areas (103, 104), and the interaction between the oxytocinergic and dopaminergic systems has been reported in several studies examining the association of OT with activity within dopaminergic regions.”
Functional Neural Plasticity and Associated Changes in Positive Affect After Compassion Training
Klimecki, O. M., Leiberg, S., Lamm, C., & Singer, T. (2013) · Cerebral Cortex · doi:10.1093/cercor/bhs142 · Cited by 634 · see citing works
Swain, J. E., Lorberbaum, J. P., Kose, S., & Strathearn, L. (2007) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2007.01731.x · Cited by 499 · see citing works
Neural correlates of long-term intense romantic love
Acevedo, B. P., Aron, A., Fisher, H. E., & Brown, L. L. (2012) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsq092 · Cited by 441 · see citing works
“We also found a correlation with activity in the PAG, an area rich in OT, AVP and opioid receptors (Jenkins et al., 1984; Loup et al., 1989; Peckys and Landwehrmeyer, 1999), associated with pain suppression (Bittar et al.”
ResultLoup, F., Tribollet, E., Dubois-Dauphin, M., & Dreifuss, J. J. (1991) · Brain Research · doi:10.1016/0006-8993(91)90345-v · Cited by 378 · see citing works
Blevins, J. E., Schwartz, M. W., & Baskin, D. G. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00604.2003 · Cited by 332 · see citing works
Immunohistochemical localization of oxytocin receptors in human brain
Boccia, M. L., Petrusz, P., Suzuki, K., Marson, L., & Pedersen, C. A. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.08.048 · Cited by 276 · see citing works
Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats
Morton, G. J., Thatcher, B. S., Reidelberger, R. D., Ogimoto, K., Wolden-Hanson, T., Baskin, D. G., Schwartz, M. W., & Blevins, J. E. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00296.2011 · Cited by 213 · see citing works
Freeman, S. M., & Young, L. J. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12382 · Cited by 196 · see citing works
“To our knowledge, rodent species with known OXTR and AVPR1a distributions include laboratory mice and rats, hamsters, guinea pigs, the socially monogamous California mouse and the promiscuous deer mouse, a social and a solitary species of tuco-tuco, two species of Central American singing mice, the eusocial naked mole…”
BackgroundInfluentialPaloyelis, Y., Doyle, O. M., Zelaya, F. O., Maltezos, S., Williams, S. C., Fotopoulou, A., & Howard, M. A. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.10.005 · Cited by 187 · see citing works
Pagani, J. H., Zhao, M., Cui, Z., Williams Avram, S. K., Caruana, D. A., Dudek, S. M., & Young, W. S. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.47 · Cited by 204 · see citing works
The effect of intranasal administration of oxytocin on fear recognition
Fischer-Shofty, M., Shamay-Tsoory, S. G., Harari, H., & Levkovitz, Y. (2010) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2009.09.003 · Cited by 184 · see citing works
MacDonald, K., & Feifel, D. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00035 · Cited by 181 · see citing works
Wigton, R., Radua, J., Allen, P., Averbeck, B., Meyer-Lindenberg, A., McGuire, P., Shergill, S. S., & Fusar-Poli, P. (2015) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.130289 · Cited by 179 · see citing works
Intranasal administration of oxytocin: behavioral and clinical effects, a review
Veening, J. G., & Olivier, B. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.04.012 · Cited by 169 · see citing works
Freeman, S. M., Walum, H., Inoue, K., Smith, A. L., Goodman, M. M., Bales, K. L., & Young, L. J. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.04.055 · Cited by 153 · see citing works
TRIBOLLET, E., DUBOIS‐DAUPHIN, M., DREIFUSS, J. J., BARBERIS, C., & JARD, S. (1992) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1992.tb34343.x · Cited by 156 · see citing works
Self-citationVariant in oxytocin receptor gene is associated with amygdala volume
Furman, D. J., Chen, M. C., & Gotlib, I. H. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.12.004 · Cited by 151 · see citing works
Intranasal oxytocin modulates EEG mu/alpha and beta rhythms during perception of biological motion
Perry, A., Bentin, S., Shalev, I., Israel, S., Uzefovsky, F., Bar-On, D., & Ebstein, R. P. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.04.011 · Cited by 143 · see citing works
Boccia, M. L., Goursaud, A.-P. S., Bachevalier, J., Anderson, K. D., & Pedersen, C. A. (2007) · Hormones and Behavior · doi:10.1016/j.yhbeh.2007.05.009 · Cited by 136 · see citing works
The role of central oxytocin in obsessive compulsive disorder and related normal behavior
Leckman, J. F., Goodman, W. K., North, W. G., Chappell, P. B., Price, L. H., Pauls, D. L., Anderson, G. M., Riddle, M. A., McDougle, C. J., Barr, L. C., et al. (1994) · Psychoneuroendocrinology · doi:10.1016/0306-4530(94)90021-3 · Cited by 133 · see citing works
Sex, Receptors, and Attachment: A Review of Individual Factors Influencing Response to Oxytocin
MacDonald, K. S. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00194 · Cited by 119 · see citing works
Freeman, S. M., Palumbo, M. C., Lawrence, R. H., Smith, A. L., Goodman, M. M., & Bales, K. L. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0315-3 · Cited by 82 · see citing works
Is oxytocin a maternal-foetal signalling molecule at birth? Implications for development
Kenkel, W. M., Yee, J. R., & Carter, C. S. (2014) · Journal of Neuroendocrinology · doi:10.1111/jne.12186 · Cited by 70 · see citing works
Neuropeptide diversity and the regulation of social behavior in New World primates
French, J. A., Taylor, J. H., Mustoe, A. C., & Cavanaugh, J. (2016) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2016.03.004 · Cited by 66 · see citing works
Sniff and mimic–Intranasal oxytocin increases facial mimicry in a sample of men
Korb, S., Malsert, J., Strathearn, L., Vuilleumier, P., & Niedenthal, P. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.06.003 · Cited by 54 · see citing works
Selective localization of oxytocin receptors and vasopressin 1a receptors in the human brainstem
Freeman, S. M., Smith, A. L., Goodman, M. M., & Bales, K. L. (2017) · Social Neuroscience · doi:10.1080/17470919.2016.1156570 · Cited by 51 · see citing works
A precision medicine approach to oxytocin trials
Andari, E., Hurlemann, R., & Young, L. J. (2017) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2017_29 · Cited by 40 · see citing works
Lee, M. R., Schwandt, M. L., Sankar, V., Suchankova, P., Sun, H., & Leggio, L. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.07.481 · Cited by 33 · see citing works
Rogers Flattery, C. N., Coppeto, D. J., Inoue, K., Rilling, J. K., Preuss, T. M., & Young, L. J. (2022) · Brain Structure and Function · doi:10.1007/s00429-021-02369-7 · Cited by 31 · see citing works
Bornemann, B., Kovacs, P., & Singer, T. (2019) · Scientific Reports · doi:10.1038/s41598-019-44201-7 · Cited by 30 · see citing works
Bridging the gap between rodents and humans: The role of non‐human primates in oxytocin research
Putnam, P. T., Young, L. J., & Gothard, K. M. (2018) · American Journal of Primatology · doi:10.1002/ajp.22756 · Cited by 28 · see citing works
“…primate species, including Titi monkeys ( Callicebus cupreus ) (Freeman, Walum, et al., 2014), marmosets ( Callithrix jacchus ) (Schorscher-Petcu, Dupré, & Tribollet, 2009), and humans (Loup, Tribollet, Dubois-Dauphin, & Dreifuss, 1991; Loup, Tribollet, Dubois-Dauphin, Pizzolato, & Dreifuss, 1989).”
Oxytocin receptors in non-human primate brain visualized with monoclonal antibody
Boccia, M. L., Panicker, A. K., Pedersen, C., & Petrusz, P. (2001) · Neuroreport · doi:10.1097/00001756-200106130-00041 · Cited by 21 · see citing works
- Authors
- Loup, F., Tribollet, E., Dubois-Dauphin, M., Pizzolato, G., & Dreifuss, J. J.
- Affiliations
- University of Geneva (CH)
- University Hospital of Geneva (CH)
- Corresponding author
- Dreifuss, J.J.
- ORCID
- Pizzolato, G.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1989-10
- Volume
- 500
- Issue
- 1-2
- Pages
- 223-230
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2084025375
- Cited by
- 136
- References
- 37
- Citations by year
- 2023: 1 · 2022: 1 · 2021: 10 · 2020: 18 · 2019: 4 · 2018: 6 · 2017: 7 · 2016: 9 · 2015: 10 · 2014: 9 · 2013: 10 · 2012: 6
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- oxytocin receptor, human brainstem, substantia nigra pars compacta, spinal trigeminal nucleus, dorsal horn, nucleus tractus solitarius, area postrema, hypoglossal nucleus, neurotransmitters, neuromodulators, human central nervous system
- MeSH terms
- Adult, Aged, Aged, 80 and over, Brain Stem, Female, Humans, Male, Middle Aged, Receptors, Angiotensin, Spinal Cord, Receptors, Oxytocin, Angiotensin Receptor Antagonists
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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
