The DOI matches its Crossref record.
Brain–Fluid Barriers: Relevance for Theoretical Controversies Regarding Vasopressin and Oxytocin Memory Research
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
Circulating OT does not easily cross the blood-brain barrier due to its relatively large molecular weight.
“First, circulating OT does not easily cross the blood-brain barrier (BBB) due to its relatively large molecular weight (McEwen, 2004).”
Citations
Cited by
Sorted by citations
Evoked axonal oxytocin release in the central amygdala attenuates fear response
Knobloch, H. S., Charlet, A., Hoffmann, L. C., Eliava, M., Khrulev, S., Cetin, A. H., Osten, P., Schwarz, M. K., Seeburg, P. H., Stoop, R., et al. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.030 · Cited by 1,049
“Systemic OT cannot pass the blood-brain barrier (McEwen, 2004), and hence, there must be central OT release.”
Oxytocin, vasopressin, and human social behavior
Heinrichs, M., von Dawans, B., & Domes, G. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.05.005 · Cited by 799
“The detailed mechanism of brain penetration of OT and AVP following different methods of administration and the relationship between plasma and central OT and AVP (including possible cross-talks of these neuropeptides at their respective central receptors) is an area that warrants further investigation [111].”
BackgroundNeuropeptides and social behaviour: effects of oxytocin and vasopressin in humans
HEINRICHS, M., & DOMES, G. (2008) · Progress in brain research · doi:10.1016/s0079-6123(08)00428-7 · Cited by 479
Modulating social behavior with oxytocin: How does it work? What does it mean?
Churchland, P. S., & Winkielman, P. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.12.003 · Cited by 464
“1 min, and transport of OXT involves a different saturable carrier (McEwen, 2004).”
BackgroundInfluentialOxytocin-dependent reopening of a social reward learning critical period with MDMA
Nardou, R., Lewis, E. M., Rothhaas, R., Xu, R., Yang, A., Boyden, E., & Dölen, G. (2019) · Nature · doi:10.1038/s41586-019-1075-9 · Cited by 334
A. Bartz, J., & Hollander, E. (2006) · Hormones and Behavior · doi:10.1016/j.yhbeh.2006.06.018 · Cited by 311
“Although there is no definitive answer to the question of how these neuropeptides cross the BBB, a number of theories have been put forward (for a thorough discussion of this topic the reader is referred to McEwen, 2004).”
BackgroundInfluentialWeisman, O., Zagoory-Sharon, O., & Feldman, R. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.06.011 · Cited by 240
Oxytocin mediates early experience-dependent cross-modal plasticity in the sensory cortices
Zheng, J.-J., Li, S.-J., Zhang, X.-D., Miao, W.-Y., Zhang, D., Yao, H., & Yu, X. (2014) · Nature Neuroscience · doi:10.1038/nn.3634 · Cited by 206
Arginine Vasopressin and Oxytocin Modulate Human Social Behavior
Ebstein, R. P., Israel, S., Lerer, E., Uzefovsky, F., Shalev, I., Gritsenko, I., Riebold, M., Salomon, S., & Yirmiya, N. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04541.x · Cited by 196
MacDonald, K., & Feifel, D. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00035 · Cited by 181
“…notion comes from recent studies in primates that found that IN OT doubles CSF OT levels within 35 min (Chang et al., 2012), strong evidence of central penetration, given that extant evidence supports that endogenous OT in the CSF derives from central not peripheral sources (McEwen, 2004).”
BackgroundInfluentialBeyond Labor: The Role of Natural and Synthetic Oxytocin in the Transition to Motherhood
Bell, A. F., Erickson, E. N., & Carter, C. S. (2014) · Journal of Midwifery & Women s Health · doi:10.1111/jmwh.12101 · Cited by 165
Buisman‐Pijlman, F. T. A., Sumracki, N. M., Gordon, J. J., Hull, P. R., Carter, C. S., & Tops, M. (2013) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2013.09.005 · Cited by 147
“McEwen (2004) reports that oxytocin seems to be transported by a saturable carrier; disappearance rate from the brain for 125I-oxytocin was 19.1 min.”
InfluentialOxytocin, vasopressin, and the motivational forces that drive social behaviors
Caldwell, H. K., & Albers, H. E. (2015) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2015_390 · Cited by 129
Adult attachment representations predict cortisol and oxytocin responses to stress
Pierrehumbert, B., Torrisi, R., Ansermet, F., Borghini, A., & Halfon, O. (2012) · Attachment & Human Development · doi:10.1080/14616734.2012.706394 · Cited by 115
“Nevertheless, it is acknowledged that there is a brain-to-blood transport of OT, across the ‘‘brain-fluid barriers’’ (McEwen, 2004).”
BackgroundQuintana, D. S., Guastella, A. J., Westlye, L. T., & Andreassen, O. A. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.166 · Cited by 107
Social Decision-Making and the Brain: A Comparative Perspective
Tremblay, S., Sharika, K. M., & Platt, M. L. (2017) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2017.01.007 · Cited by 113
Quintana, D. S., Westlye, L. T., Alnæs, D., Rustan, Ø. G., Kaufmann, T., Smerud, K. T., Mahmoud, R. A., Djupesland, P. G., & Andreassen, O. A. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.04.010 · Cited by 102
Intranasal oxytocin effects on social cognition: A critique
Evans, S. L., Dal Monte, O., Noble, P., & Averbeck, B. B. (2014) · Brain Research · doi:10.1016/j.brainres.2013.11.008 · Cited by 97
“Since OT is a relatively large, hydrophilic molecule, blood–brain penetration is too poor to cause any measurable effects on central systems (McEwen, 2004), so peripheral OT likely re-enters the brain in negligible amounts.”
Stragier, B., Bundel, D. D., Sarre, S., Smolders, I. J., Vauquelin, G., Dupont, A. G., Michotte, Y. M., & Vanderheyden, P. (2007) · Heart Failure Reviews · doi:10.1007/s10741-007-9062-x · Cited by 95
Husarova, V. M., Lakatošová, S., Pivovarciova, A., Babinská, K., Bakoš, J., Durdiaková, J., Kubranská, A., Ondrejka, I., & Ostatníková, D. (2016) · Psychiatry Investigation · doi:10.4306/pi.2016.13.2.174 · Cited by 82
Hicks, C., Ramos, L., Reekie, T., Misagh, G. H., Narlawar, R., Kassiou, M., & McGregor, I. S. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12613 · Cited by 76
“There is increasing evidence that circulating OT directly penetrates the blood–brain barrier in small, but physiologically significant amounts (Neumann et al., 2013), and may also indirectly increase brain OT levels via stimulation of vagal afferents (McEwen, 2004).”
BackgroundChristensen, J. C., Shiyanov, P. A., Estepp, J. R., & Schlager, J. J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0116172 · Cited by 69
“However, there is evidence for complex feedback both within the periphery and between the CNS and the periphery [3, 11] that can result in coordinated, though not coupled, release [15].”
BackgroundOxytocin: Parallel Processing in the Social Brain?
Dölen, G. (2015) · Journal of Neuroendocrinology · doi:10.1111/jne.12284 · Cited by 65
The Roles of Oxytocin and CD38 in Social or Parental Behaviors
Lopatina, O. L., Ивановна, И. А., Salmina, A. B., & Higashida, H. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00182 · Cited by 66
“As expected, human studies showed that plasma and salivary OXT levels in mothers are associated with parent and child’s social engagement, affect synchrony, and positive communicative sequences between the parent and child (Feldman and Eidelman, 2003; Feldman et al.,”
BackgroundRault, J. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.03.015 · Cited by 64
Arginine Vasotocin Regulation of Interspecific Cooperative Behaviour in a Cleaner Fish
Soares, M. C., Bshary, R., Mendonça, R., Grutter, A. S., & Oliveira, R. F. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039583 · Cited by 60
“In mammals, neuropeptides are unable cross the blood-brain barrier under regular physiological conditions [46].”
BackgroundA Role for Oxytocin in the Etiology and Treatment of Schizophrenia
Rich, M. E., & Caldwell, H. K. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00090 · Cited by 60
“Previous work found that injections of Oxt reduce the symptoms of psychosis and anhedonia in patients with schizophrenia (62, 63).”
BackgroundEndogenous oxytocin, cortisol, and testosterone in response to group singing
Bowling, D. L., Gahr, J., Ancochea, P. G., Hoeschele, M., Canoine, V., Fusani, L., & Fitch, W. T. (2022) · Hormones and Behavior · doi:10.1016/j.yhbeh.2021.105105 · Cited by 51
Hicks, C., Cornish, J. L., Baracz, S. J., Suraev, A. S., & McGregor, I. S. (2014) · Addiction Biology · doi:10.1111/adb.12197 · Cited by 52
“Recent studies suggest that physiologically relevant amounts of peripherally delivered OT do influence the brain either directly (Neumann et al. 2013), or indirectly via stimulation of vagal afferents (McEwen 2004).”
BackgroundBDNF-TrkB signaling in oxytocin neurons contributes to maternal behavior
Maynard, K. R., Hobbs, J. W., Phan, B. N., Gupta, A., Rajpurohit, S., Williams, C. A., Rajpurohit, A., Shin, J. H., Jaffe, A. E., & Martinowich, K. (2018) · eLife · doi:10.7554/elife.33676 · Cited by 47
“Given that OXT is of great interest for therapeutic intervention but does not easily cross the blood brain barrier (Landgraf, Ermisch, & Hess, 1979; McEwen, 2004), the molecular profile of OXT neurons presented here provides a valuable resource for probing gene pathways critical for OXT expression and regulation.”
BackgroundYeomans, D. C., Hanson, L. R., Carson, D. S., Tunstall, B. J., Lee, M. R., Tzabazis, A., Jacobs, D. L., & Frey, W. H. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01511-7 · Cited by 42
Excitation of Tuberoinfundibular Dopamine Neurons by Oxytocin: Crosstalk in the Control of Lactation
Briffaud, V., Williams, P., Courty, J., & Broberger, C. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.2633-14.2015 · Cited by 37
“Circulating OT penetrates the blood– brain barrier poorly (Ermisch et al., 1985; McEwen, 2004) and so is unlikely to act directly on TIDA neurons as the dmArc is likely to lie within this barrier (Smith and Ferguson, 2014).”
BackgroundIntertwined associations between oxytocin, immune system and major depressive disorder
Jiang, J., Yang, M., Tian, M., Chen, Z., Xiao, L., & Gong, Y. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114852 · Cited by 40
“Prior studies have shown that individuals with MDD exhibit abnormal concentrations of urate and albumin in both cerebrospinal fluid and blood, indicating BBB impairment [124].”
BackgroundInfluentialThe impact of oxytocin on neurite outgrowth and synaptic proteins in Magel2 ‐deficient mice
Reichova, A., Schaller, F., Bukatová, S., Bačová, Z., Muscatelli, F., & Bakoš, J. (2021) · Developmental Neurobiology · doi:10.1002/dneu.22815 · Cited by 36
Modi, M. E., Majchrzak, M. J., Fonseca, K. R., Doran, A., Osgood, S., Vanase-Frawley, M., Feyfant, E., McInnes, H., Darvari, R., Buhl, D. L., et al. (2016) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.116.232702 · Cited by 29
“(Fabian et al., 1969; Landgraf, 1981; Ermisch et al., 1985; McEwen, 2004).”
BackgroundOxytocin and Addiction: Potential Glutamatergic Mechanisms
Sundar, M., Patel, D., Young, Z., & Leong, K.-C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052405 · Cited by 31
“However, some have questioned whether the systemic administration of OXT actually allows for the compound to reach the brain in sufficient amounts, due to the challenge posed by the blood–brain barrier (BBB).”
BackgroundInfluentialMeasuring peripheral oxytocin and vasopressin in nonhuman primates
Ziegler, T. E. (2018) · American Journal of Primatology · doi:10.1002/ajp.22871 · Cited by 25
“Once released into circulation, less than 1% will penetrate the blood–brain barrier and access the central nervous system (McEwen, 2004).”
BackgroundL’ocytocine et la dépression du post-partum
Cardaillac, C., Rua, C., Simon, E. G., & El‐Hage, W. (2016) · Journal de gynécologie, obstétrique et biologie de la reproduction. Supplément/Journal de gynécologie obstétrique et biologie de la reproduction · doi:10.1016/j.jgyn.2016.05.002 · Cited by 23
Oxytocin therapy in hypopituitarism: Challenges and opportunities
Bhargava, R., Daughters, K., & Rees, A. (2018) · Clinical Endocrinology · doi:10.1111/cen.13909 · Cited by 22
Investigational drugs for alcohol use disorders: a review of preclinical data
Ch’ng, S. S., & Lawrence, A. J. (2018) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2018.1472763 · Cited by 14
“Several hypotheses for how OT crosses the blood–brain barrier have been put forth (see [74] for review).”
BackgroundEngel, S., van Zuiden, M., Frijling, J. L., Koch, S. B. J., Nawijn, L., Yildiz, R. L. W., Schumacher, S., Knaevelsrud, C., Bosch, J. A., Veltman, D. J., et al. (2020) · European Journal of Psychotraumatology · doi:10.1080/20008198.2020.1761622 · Cited by 14
“In this regard, as GR feedback sensitivity and oxytocin impact memory consolidation and retrieval (de Quervain, Schwabe, & Roozendaal, 2017; McEwen, 2004), it seems interesting to investigate their effects with regard to the development of intrusions specifically.”
BackgroundHormones and Economic Decisions
Nadler, A., & Zak, P. J. (2016) · Studies in neuroscience, psychology and behavioral economics · doi:10.1007/978-3-642-35923-1_3 · Cited by 9
Design and Fabrication of Brain-Targeted Drug Delivery
Soni, V., Pandey, V., Asati, S., Jain, P., & Tekade, R. K. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-817909-3.00014-5 · Cited by 14
Dumais, K. M., & Veenema, A. H. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-802114-9.00011-1 · Cited by 11
Sheng, W., Harden, S. W., Tan, Y., Krause, E. G., & Frazier, C. J. (2021) · eLife · doi:10.7554/elife.63486 · Cited by 7
“However, effective therapeutic delivery of exogenous OTR agonists into the CNS of humans remains difficult (Ermisch et al., 1985; McEwen, 2004; Veening and Olivier, 2013; Leng and Ludwig, 2016; Sheng et al. eLife 2021;10:e63486.”
BackgroundWolfe, M., Wisniewska, H., Tariga, H., Ibanez, G., Collins, J. C., Wiśniewski, K., Qi, S., Srinivasan, K., Hargrove, D. M., & Lindstrom, B. (2018) · Neuropeptides · doi:10.1016/j.npep.2018.05.007 · Cited by 5
Winterdahl, M., Nielsen, E. N., Hansen, S. B., Dias, A. H., Vendelbo, M. H., Jakobsen, S., & Yeomans, D. C. (2025) · EJNMMI Research · doi:10.1186/s13550-025-01329-0 · Cited by 4
“As oxytocin is rapidly metabolised in the blood [28], and has limited capacity to cross the blood–brain barrier once in the blood [19], the capacity to bypass systemic circulation and directly reach neural targets via intra-nasal delivery holds significant promise for therapeutic interventions that…”
Beyond Labor: The Role of Natural and Synthetic Oxytocin in the Transition to Motherhood (2014/023)
(2014) · Journal of Midwifery & Women s Health · doi:10.1111/jmwh.12182 · Cited by 4
Nasal Oxytocin: Facts and Routes
Lima, J. P. C., & Rodrigues, A. L. (2019) · Acta Psychopathologica · doi:10.4172/2469-6676.100181 · Cited by 3
Central modulation of affective touch, pain, and emotion in humans
Ellingsen, D. (2014) · Cited by 2
Polk, R. J., Wright, K. A., Lin, T., Krol, K. M., Perkeybile, A. M., Nazarloo, H. P., Carter, C. S., Connelly, J. J., & Ebner, N. C. (2025) · Scientific Reports · doi:10.1038/s41598-025-07353-3 · Cited by 2
A Review of the Potential Therapeutic Application of Vagus Nerve Stimulation During Childbirth
Enderli, T. (2017) · Cited by 1
Hypothalamic Neuropeptides and the Blood—Brain Barrier
Begley, D. J. (2006) · Elsevier eBooks · doi:10.1016/b978-012369442-3/50208-7 · Cited by 1
Begley, D. J. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-385095-9.00228-1
The relationship between oxytocin pathway genes and personality traits and psychosis characteristics
Haram, M. (2017) · NORA - Norwegian Open Research Archives
Lima, J. P. C. (2018) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.47.2018.tde-19042018-161017
L’ocytocine et la dépression du post-partum
Cardaillac, C., Rua, C., Simon, E. G., & El‐Hage, W. (2017) · Sages-Femmes · doi:10.1016/j.sagf.2017.04.005
“Mais, a barrière hémato-encéphalique possède des systèmes de ransport sélectifs actifs de molécules hydrophiles, et pluieurs études ont émis l’hypothèse qu’il puisse exister un ransport d’oxytocine et d’AVP actif du sang vers le liquide érébro-spinal [75].”
Bothwell, M. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733954343.793564946
Zhang, Y., Pu, J., Shen, Z., Zhang, Y., Liu, J., Zhang, D., Deng, K., & Yao, Y. (2026) · World Neurosurgery · doi:10.1016/j.wneu.2026.125172
Metadata
- Authors
- McEwen, B. B.
- Affiliations
- Southern Connecticut State University (US)
- Corresponding author
- McEwen, Barbara B.
- Venue
- Advances in pharmacology
- Publisher
- Elsevier
- Published
- 2004
- Volume
- 50
- Pages
- 531-592
- ISSN
- 1054-3589 (ISSN-L)
- OpenAlex
- W1596239931
- Cited by
- 59
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 5 · 2012: 4
- FWCI
- 2.41
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Advances in pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Keywords
- vasopressin, oxytocin, blood-brain barrier, blood-CSF barrier, cerebrospinal fluid, peptide transport, memory, brain capillary endothelium
- MeSH terms
- Animals, Arginine Vasopressin, Blood-Brain Barrier, Humans, Memory, Oxytocin, Vasopressins
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
