Aerosolized oxytocin increases cerebrospinal fluid oxytocin in rhesus macaques
Open accessAbstract
Intranasal (IN) administration is a widely used method for examining the effect of oxytocin (OT) on social behavior and cognition in healthy subjects and psychiatric populations. IN-OT in humans enhances trust, emotional perception, and empathetic behavior and is under investigation as a potential pharmacotherapy to enhance social functioning in a variety of neuropsychiatric disorders, including autism spectrum disorders (ASD). Nonhuman primates (NHP) are an important model for understanding the effect of OT on social cognition, its neural mechanisms, and the development of IN-OT as a pharmacotherapy for treating social deficits in humans. However, NHP and even some human populations, such as very young infants and children, cannot easily follow the detailed self-administration protocol used in the majority of human IN-OT studies. Therefore, we evaluated the efficacy of several OT-administration routes for elevating central OT concentrations in rhesus macaques. First, we examined the effect of IN and intravenous (IV) routes of OT administration on concentrations of OT and vasopressin (AVP) in plasma and lumbar CSF. Second, we examined these same measures in monkeys after an aerosolized (AE) OT delivery route. All three administration routes significantly increased plasma OT concentrations, but only the AE-OT route significantly increased concentrations of CSF OT. No route affected concentrations of AVP in plasma or CSF. This study confirms that the AE route is the most effective method for increasing central OT concentrations in monkeys, and may also be an effective route, alternative to IN, for administering OT to some human populations.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In macaques given 24 IU oxytocin, only aerosol produced a significant CSF increase (from about 20 to about 60 pg/ml); both spray and aerosol raised plasma oxytocin, and the same dose intravenously raised plasma to about 60,000 pg/ml without increasing CSF.
“In a larger study, Modi et al. gave 24IU oxytocin (~5µg/kg body weight) to macaques by spray or aerosol; only the aerosol produced a significant increase in CSF (from ~20 to ~60pg/ml) (25).”
From Intranasal Oxytocin: Myths and Delusions (2016) · cites this paper as [25]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe intranasal dose administered in the present study has been associated with changes in central function in humans, and similar or smaller doses of oxytocin or vasopressin have been associated with elevations in peptide levels in the cerebrospinal fluid in humans or macaques of no more than approximately 55 pg/ml or up to 0.005% of the administered dose.
“The intranasal dose administered in the present study has been associated with changes in central function in humans 58, and similar or smaller doses of oxytocin or vasopressin (24–48 IU for oxytocin; 40–80 IU for vasopressin) have been associated with elevations in peptide levels in the cerebrospinnal fluid in humans or macaques of no more than approximately 55 pg/ml in actual levels 70, 71, 72,”
From The Analgesic Effect of Oxytocin in Humans: A Double‐Blind, Placebo‐Controlled Cross‐Over Study Using Laser‐Evoked Potentials (2016) · cites this paper as [72]
Intranasal oxytocin leads to a significant increase in oxytocin concentrations in cerebrospinal fluid.
“In addition, several studies have found that IN-OT leads to a significant increase in OT concentrations in cerebrospinal fluid, which may also be indicative of IN-OT reaching the brain [30, 31].”
From Salivary oxytocin concentrations in males following intranasal administration of oxytocin: a double-blind, cross-over study (2015) · cites this paper as [31]
In monkeys, intranasal oxytocin or oxytocin intake via a nebulizer at 25 or 48 IU increased cerebrospinal fluid oxytocin concentration compared with placebo.
“Also, in monkeys, IN-OT or OT intake via a nebulizer (25 or 48 IU) increased OT CSF concentration compared to placebo (Chang et al. 2012; Dal Monte et al. 2014; Modi et al. 2014).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Modi et al. 2014
Even if OT does travel across the BBB in small amounts, this quantity is not large enough to dampen amygdala activity compared to placebo.
“While there is conflicting evidence on whether peripheral OT can cross the BBB (Modi et al., 2014), our study suggests that even if OT does travel across this barrier in small amounts, this quantity is not large enough to dampen amygdala activity compared to placebo.”
From Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial (2016) · cites this paper as Modi et al., 2014
The immediate influence of intranasal oxytocin on psychopathology and brain function is supported by primate studies showing intranasal oxytocin reaches cerebrospinal fluid.
“The here-observed immediate influence of intranasal oxytocin on psychopathology and hence on brain function is supported by primate studies showing that intranasal oxytocin, such as other intranasally administered anxiolytic neuropeptides like NPS [45], are able to reach the cerebrospinal fluid [46, 47] and thus, assumingly, also the brain.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Oxytocin increases trust in humans
Kosfeld, M., Heinrichs, M., Zak, P. J., Fischbacher, U., & Fehr, E. (2005) · Nature · doi:10.1038/nature03701 · Cited by 3,690 · see citing works
Oxytocin, vasopressin, and the neurogenetics of sociality
Donaldson, Z. R., & Young, L. J. (2008) · Science · doi:10.1126/science.1158668 · Cited by 1,645 · see citing works
Sniffing neuropeptides: A transnasal approach to the human brain
Born, J., Lange, T., Kern, W., McGregor, G. P., Bickel, U., & Fehm, H. L. (2002) · Nature Neuroscience · doi:10.1038/nn0602-849 · Cited by 1,356 · see citing works
Intranasal delivery of biologics to the central nervous system
Lochhead, J. J., & Thorne, R. G. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.11.002 · Cited by 1,214 · see citing works
Landgraf, R., & Neumann, I. D. (2004) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2004.05.001 · Cited by 1,059 · see citing works
Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders.
Guastella, A. J., Einfeld, S. L., Gray, K. M., Rinehart, N. J., Tonge, B. J., Lambert, T. J., & Hickie, I. B. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.020 · Cited by 962 · see citing works
Neumann, I. D., & Landgraf, R. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.08.004 · Cited by 954 · see citing works
Promoting social behavior with oxytocin in high-functioning autism spectrum disorders.
Andari, E., Duhamel, J.-R., Zalla, T., Herbrecht, E., Leboyer, M., & Sirigu, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910249107 · Cited by 941 · see citing works
Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior
Ross, H. E., & Young, L. J. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.05.004 · Cited by 856 · cited 2× · see citing works
“For example, in animals OTenhances social information processing, social recognition, maternal care, and social attachment through actions on central OTreceptors (Ross and Young, 2009).”
Oxytocin increases gaze to the eye region of human faces
Guastella, A. J., Mitchell, P. B., & Dadds, M. R. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.06.026 · Cited by 798 · see citing works
Plasma oxytocin levels in autistic children
Modahl, C., Green, L. A., Fein, D., Morris, M., Waterhouse, L., Feinstein, C., & Levin, H. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(97)00439-3 · Cited by 728 · see citing works
Oxytocin Increases Retention of Social Cognition in Autism
Hollander, E., Bartz, J., Chaplin, W., Phillips, A., Sumner, J., Soorya, L., Anagnostou, E., & Wasserman, S. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.05.030 · Cited by 693 · see citing works
Oxytocin Infusion Reduces Repetitive Behaviors in Adults with Autistic and Asperger's Disorders
Hollander, E., Novotny, S., Hanratty, M., Yaffe, R., DeCaria, C. M., Aronowitz, B. R., & Mosovich, S. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300021 · Cited by 689 · see citing works
Genomic and epigenetic evidence for oxytocin receptor deficiency in autism
Gregory, S. G., Connelly, J. J., Towers, A. J., Johnson, J., Biscocho, D., Markunas, C. A., Lintas, C., Abramson, R. K., Wright, H. H., Ellis, P., et al. (2009) · BMC Medicine · doi:10.1186/1741-7015-7-62 · Cited by 576 · see citing works
Positive Association of the Oxytocin Receptor Gene (OXTR) with Autism in the Chinese Han Population
Wu, S., Jia, M., Ruan, Y., Liu, J., Guo, Y., Mei, S., Gong, X., Zhang, Y., Yang, X., & Zhang, D. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.03.013 · Cited by 553 · see citing works
Effects of intranasal oxytocin on emotional face processing in women
Domes, G., Lischke, A., Berger, C., Grossmann, A., Hauenstein, K., Heinrichs, M., & Herpertz, S. C. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.06.016 · Cited by 521 · cited 2× · see citing works
“These studies report numerous effects of IN-OT on human social cognition, including enhanced eye gaze, increased trust, better recognition of facial emotions, improved face memory, and empathy (Domes et al., 2010; Guastella and MacLeod, 2012; Guastella et al., 2008; Kosfeld et al., 2005; Rimmele et al., 2009; Savaskan…”
Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice
Neumann, I. D., Maloumby, R., Beiderbeck, D. I., Lukas, M., & Landgraf, R. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.03.003 · Cited by 511 · see citing works
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 · see citing works
Striepens, N., Kendrick, K. M., Hanking, V., Landgraf, R., Wüllner, U., Maier, W., & Hurlemann, R. (2013) · Scientific Reports · doi:10.1038/srep03440 · Cited by 452 · see citing works
Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism
Jacob, S., Brune, C. W., Carter, C. S., Leventhal, B. L., Lord, C., & Cook, E. H. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.02.001 · Cited by 425 · see citing works
Oxytocin Makes a Face in Memory Familiar
Rimmele, U., Hediger, K., Heinrichs, M., & Klaver, P. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4260-08.2009 · Cited by 402 · see citing works
Graustella, A. J., & MacLeod, C. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.01.002 · Cited by 379 · see citing works
Mens, W. B. J., Witter, A., & Van Wimersma Greidanus, T. B. (1983) · Brain Research · doi:10.1016/0006-8993(83)90478-x · Cited by 360 · see citing works
Guastella, A. J., Hickie, I. B., McGuinness, M. M., Otis, M., Woods, E. A., Disinger, H. M., Chan, H.-K., Chen, T. F., & Banati, R. B. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.11.019 · Cited by 357 · see citing works
Anagnostou, E., Soorya, L., Chaplin, W., Bartz, J., Halpern, D., Wasserman, S., Wang, A. T., Pepa, L., Tanel, N., Kushki, A., et al. (2012) · Molecular Autism · doi:10.1186/2040-2392-3-16 · Cited by 350 · see citing works
Lerer, E., Levi, S., Salomon, S., Darvasi, A., Yirmiya, N., & Ebstein, R. P. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002087 · Cited by 349 · see citing works
Post-learning intranasal oxytocin modulates human memory for facial identity
Savaskan, E., Ehrhardt, R., Schulz, A., Walter, M., & Schächinger, H. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2007.12.004 · Cited by 262 · see citing works
Chang, S. W. C., Barter, J. W., Ebitz, R. B., Watson, K. K., & Platt, M. L. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114621109 · Cited by 252 · cited 2× · see citing works
“This route has been shown to elicit effects on social behavior and perception in monkeys in three separate studies (Chang et al., 2012; Ebitz et al., 2013; Parr et al., 2013).”
Neumann, I., Ludwig, M., Engelmann, M., Pittman, Q. J., & Landgraf, R. (2008) · Neuroendocrinology · doi:10.1159/000126604 · Cited by 236 · see citing works
The oxytocin system in drug discovery for autism: Animal models and novel therapeutic strategies
Modi, M. E., & Young, L. J. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.12.010 · Cited by 218 · see citing works
Social attention and the brain
Klein, J. T., Shepherd, S. V., & Platt, M. L. (2009) · Current Biology · doi:10.1016/j.cub.2009.08.010 · Cited by 196 · see citing works
Freeman, S. M., Inoue, K., Smith, A. L., Goodman, M. M., & Young, L. J. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.03.023 · Cited by 185 · cited 1× · see citing works
“Moreover, the neuroanatomical distribution of OTreceptors in rhesus macaques have recently been described, providing insights into the sites of OT action in the brain in this nonhuman primate (NHP) model organisms (Freeman et al., 2014).”
The acute effects of intranasal oxytocin administration on endocrine and sexual function in males
Burri, A., Heinrichs, M., Schedlowski, M., & Kruger, T. H. C. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.01.014 · Cited by 168 · 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
Tachibana, M., Kagitani-Shimono, K., Mohri, I., Yamamoto, T., Sanefuji, W., Nakamura, A., Oishi, M., Kimura, T., Onaka, T., Ozono, K., et al. (2013) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2012.0048 · Cited by 151 · see citing works
Neumann, I. D., Koehler, E., Landgraf, R., & Summy‐Long, J. Y. (1994) · Endocrinology · doi:10.1210/endo.134.1.8275928 · Cited by 146 · see citing works
Suman, J., Laube, B. L., & Dalby, R. N. (1999) · Pharmaceutical Research · doi:10.1023/a:1011933410898 · Cited by 141 · see citing works
Oxytocin and experimental therapeutics in autism spectrum disorders
BARTZ, J., & HOLLANDER, E. (2008) · Progress in Brain Research · doi:10.1016/s0079-6123(08)00435-4 · Cited by 139 · see citing works
Intranasal drug targeting of hypocretin-1 (orexin-A) to the central nervous system
Dhuria, S. V., Hanson, L. R., & Frey, W. H. (2008) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21604 · Cited by 135 · see citing works
Oxytocin blunts social vigilance in the rhesus macaque
Ebitz, R. B., Watson, K. K., & Platt, M. L. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1305230110 · Cited by 132 · see citing works
Intranasal oxytocin selectively attenuates rhesus monkeys’ attention to negative facial expressions
Parr, L. A., Modi, M., Siebert, E., & Young, L. J. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.02.011 · Cited by 124 · see citing works
(1985) · PubMed · Cited by 104 · see citing works
Effects of Anatomy and Particle Size on Nasal Sprays and Nebulizers
Frank-Ito, D. O., Kimbell, J. S., Pawar, S. S., & Rhee, J. S. (2011) · Otolaryngology · doi:10.1177/0194599811427519 · Cited by 87 · see citing works
Editorial comment: Oxytocin, vasopressin and social behavior
Young, L. J., & Flanagan-Cato, L. M. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.02.019 · Cited by 81 · see citing works
Nasal-to-CNS Drug Delivery: Where are We Now and Where are We heading? an Industrial Perspective
Landis, M. S., Boyden, T. L., & Pegg, S. (2012) · Therapeutic Delivery · doi:10.4155/tde.11.149 · Cited by 64 · see citing works
Comparative pathology of the nasal mucosa in laboratory animals exposed to inhaled irritants.
Harkema, J. R. (1990) · Environmental Health Perspectives · doi:10.1289/ehp.85-1568334 · Cited by 52 · see citing works
Plasma Oxytocin Concentrations in Man after Different Routes of Administration of Synthetic Oxytocin
Landgraf, R. (2009) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0029-1210444 · Cited by 51 · see citing works
Self-citationComparative Pathology of the Nasal Mucosa in Laboratory Animals Exposed to Inhaled Irritants
Harkema, J. R. (1990) · Environmental Health Perspectives · doi:10.2307/3430686 · Cited by 49 · see citing works
Neumann, I. D., Torner, L., Toschi, N., & Veenema, A. H. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00763.2005 · Cited by 43 · see citing works
Somatodendritic autoreceptors on oxytocin neurones.
Freund‐Mercier, M. J., & Stoeckel, M. E. (1995) · PubMed · Cited by 34 · see citing works
Altner, H., & Altner-Kolnberger, I. (1974) · Cell and Tissue Research · doi:10.1007/bf00221071 · Cited by 25 · see citing works
橘, 雅. (2014) · Medical Entomology and Zoology · Cited by 13 · see citing works
Flagged first, then by citations
1 of the 53 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Parr LA Modi ME Siebert E Young LJ 2013b Intranasal oxytocin selectively attenuates rhesus monkeys’ attention to negative facial expressions Psychoneuroendocrinology PMC3743934 23490074
Cited by
Sorted by citations
The oxytocin receptor: from intracellular signaling to behavior
Jurek, B., & Neumann, I. D. (2018) · Physiological Reviews · doi:10.1152/physrev.00031.2017 · Cited by 999 · see citing works
Intranasal Oxytocin: Myths and Delusions
Leng, G., & Ludwig, M. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.05.003 · Cited by 615 · see citing works
Dumais, K. M., & Veenema, A. H. (2016) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2015.04.003 · Cited by 520 · see citing works
“Indeed, intranasal OT administration also leads to increases in OT in plasma and saliva in humans (Gossen et al., 2012; van Ijzendoorn et al., 2012) and rhesus macaques (Modi et al., 2014).”
BackgroundThe biology of mammalian parenting and its effect on offspring social development
Rilling, J. K., & Young, L. J. (2014) · Science · doi:10.1126/science.1252723 · Cited by 452 · see citing works
Self-citationDoes Oxytocin Increase Trust in Humans? A Critical Review of Research
Nave, G., Camerer, C., & McCullough, M. (2015) · Perspectives on Psychological Science · doi:10.1177/1745691615600138 · Cited by 309 · see citing works
Quintana, D. S., Lischke, A., Grace, S., Scheele, D., Ma, Y., & Becker, B. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00864-7 · Cited by 263 · see citing works
Lee, M. R., Scheidweiler, K. B., Diao, X. X., Akhlaghi, F., Cummins, A., Huestis, M. A., Leggio, L., & Averbeck, B. B. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.27 · Cited by 235 · see citing works
Kinetics and dose dependency of intranasal oxytocin effects on amygdala reactivity
Spengler, F. B., Schultz, J., Scheele, D., Essel, M., Maier, W., Heinrichs, M., & Hurlemann, R. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.04.015 · Cited by 229 · see citing works
Freeman, S. M., Inoue, K., Smith, A. L., Goodman, M. M., & Young, L. J. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.03.023 · Cited by 185 · see citing works
“More recently, IN-OT administration in rhesus macaques has been shown to increase central OT concentrations (Chang et al., 2012) (Modi et al., 2014) and to affect a variety of social behaviors including increasing gaze to the eye region of monkey faces (Ebitz et al., 2013), increasing both selfish…”
BackgroundPaloyelis, 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
CSF and blood oxytocin concentration changes following intranasal delivery in macaque
Dal Monte, O., Noble, P. L., Turchi, J., Cummins, A., & Averbeck, B. B. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103677 · Cited by 177 · see citing works
Translational Mouse Models of Autism: Advancing Toward Pharmacological Therapeutics
Kazdoba, T. M., Leach, P. T., Yang, M., Silverman, J. L., Solomon, M., & Crawley, J. N. (2015) · Current topics in behavioral neurosciences · doi:10.1007/7854_2015_5003 · Cited by 172 · see citing works
McCormack, S. E., Blevins, J. E., & Lawson, E. A. (2019) · Endocrine Reviews · doi:10.1210/endrev/bnz012 · Cited by 140 · see citing works
Effects of oxytocin administration on spirituality and emotional responses to meditation
Cappellen, P. V., Way, B. M., Isgett, S. F., & Fredrickson, B. L. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsw078 · Cited by 138 · see citing works
Blevins, J. E., & Baskin, D. G. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.05.023 · Cited by 132 · see citing works
Labeled oxytocin administered via the intranasal route reaches the brain in rhesus macaques
Lee, M. R., Shnitko, T. A., Blue, S. W., Kaucher, A. V., Winchell, A. J., Erikson, D. W., Grant, K. A., & Leggio, L. (2020) · Nature Communications · doi:10.1038/s41467-020-15942-1 · Cited by 132 · see citing works
Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques
Freeman, S. M., Samineni, S., Allen, P. C., Stockinger, D., Bales, K. L., Hwa, G. G. C., & Roberts, J. A. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.01.014 · Cited by 128 · see citing works
Overview of human oxytocin research
Kendrick, K. M., Guastella, A. J., & Becker, B. (2017) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2017_19 · Cited by 121 · see citing works
Smith, A. S., Korgan, A. C., & Young, W. S. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104324 · Cited by 107 · see citing works
Quintana, D. S., Guastella, A. J., Westlye, L. T., & Andreassen, O. A. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.166 · Cited by 107 · see citing works
Oxytocin for the treatment of drug and alcohol use disorders
Lee, M. R., & Weerts, E. M. (2016) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000258 · Cited by 105 · see citing works
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 105 · see citing works
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 · see citing works
Oxytocin and stress-related disorders: neurobiological mechanisms and treatment opportunities
Sippel, L. M., Allington, C. E., Pietrzak, R. H., Harpaz-Rotem, I., Mayes, L. C., & Olff, M. (2017) · Chronic Stress · doi:10.1177/2470547016687996 · Cited by 99 · see citing works
The role of oxytocin in regulation of appetitive behaviour, body weight and glucose homeostasis
Lawson, E. A., Olszewski, P. K., Weller, A., & Blevins, J. E. (2019) · Journal of Neuroendocrinology · doi:10.1111/jne.12805 · Cited by 97 · see citing works
Evidence for Intranasal Oxytocin Delivery to the brain: Recent Advances and Future Perspectives
Quintana, D. S., Smerud, K. T., Andreassen, O. A., & Djupesland, P. G. (2018) · Therapeutic Delivery · doi:10.4155/tde-2018-0002 · Cited by 94 · see citing works
Daughters, K., Manstead, A. S. R., Hubble, K., Rees, A., Thapar, A., & van Goozen, S. H. M. (2015) · PLOS ONE · doi:10.1371/journal.pone.0145104 · Cited by 92 · see citing works
“In addition, several studies have found that IN-OT leads to a significant increase in OT concentrations in cerebrospinal fluid, which may also be indicative of IN-OT reaching the brain [30, 31].”
BackgroundCalcagnoli, F., Kreutzmann, J. C., de Boer, S. F., Althaus, M., & Koolhaas, J. M. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.09.019 · Cited by 92 · see citing works
Alvares, G. A., Quintana, D. S., & Whitehouse, A. J. O. (2017) · Autism Research · doi:10.1002/aur.1692 · Cited by 91 · see citing works
Oxytocin effects in schizophrenia: Reconciling mixed findings and moving forward
Bradley, E., & Woolley, J. D. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.05.007 · Cited by 88 · see citing works
Oxytocin promotes coordinated out-group attack during intergroup conflict in humans
Zhang, H., Gross, J., De Dreu, C., & Ma, Y. (2019) · eLife · doi:10.7554/elife.40698 · Cited by 87 · see citing works
Modi, M. E., Inoue, K., Barrett, C. E., Kittelberger, K. A., Smith, D. G., Landgraf, R., & Young, L. J. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.35 · Cited by 82 · see citing works
Inhaled oxytocin increases positive social behaviors in newborn macaques
Simpson, E. A., Sclafani, V., Paukner, A., Hamel, A. F., Novak, M. A., Meyer, J. S., Suomi, S. J., & Ferrari, P. F. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402471111 · Cited by 82 · see citing works
A, T. R. D. J., & Neumann, I. D. (2017) · Current topics in behavioral neurosciences · doi:10.1007/7854_2017_13 · Cited by 74 · see citing works
Chang, S. W. C., & Platt, M. L. (2014) · Brain Research · doi:10.1016/j.brainres.2013.11.006 · Cited by 71 · see citing works
Oxytocin promotes intuitive rather than deliberated cooperation with the in-group
Ten Velden, F. S., Daughters, K., & De Dreu, C. K. W. (2017) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.06.005 · Cited by 66 · see citing works
Oxytocin modulates fMRI responses to facial expression in macaques
Liu, N., Hadj-Bouziane, F., Jones, K. B., Turchi, J. N., Averbeck, B. B., & Ungerleider, L. G. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1508097112 · Cited by 65 · see citing works
Oxytocin: Parallel Processing in the Social Brain?
Dölen, G. (2015) · Journal of Neuroendocrinology · doi:10.1111/jne.12284 · Cited by 65 · see citing works
Jiang, Y., & Platt, M. L. (2018) · Scientific Reports · doi:10.1038/s41598-018-25607-1 · Cited by 66 · see citing works
Oxytocin, social cognition and psychiatry
Young, L. J. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2014.186 · Cited by 64 · see citing works
Self-citationTargeting the Oxytocin System: New Pharmacotherapeutic Approaches
Gulliver, D. W., Werry, E. L., Reekie, T. A., Katte, T. A., Jorgensen, W. T., & Kassiou, M. (2018) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2018.11.001 · Cited by 63 · see citing works
Horta, M., Kaylor, K., Feifel, D., & Ebner, N. C. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.10.012 · Cited by 62 · see citing works
Rault, J. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.03.015 · Cited by 63 · see citing works
Paloyelis, Y., Krahé, C., Maltezos, S., Williams, S. C., Howard, M. A., & Fotopoulou, A. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12347 · Cited by 61 · see citing works
Oxytocin as Treatment for Social Cognition, Not There Yet
Erdozain, A. M., & Peñagarikano, O. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00930 · Cited by 61 · see citing works
Ferris, C. F., Yee, J. R., Kenkel, W. M., Dumais, K. M., Moore, K., Veenema, A. H., Kulkarni, P. P., Perkybile, A. M., & Carter, C. S. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00245 · Cited by 60 · see citing works
Current findings on the role of oxytocin in the regulation of food intake
Spetter, M. S., & Hallschmid, M. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.03.007 · Cited by 58 · see citing works
Sack, M., Spieler, D., Wizelman, L., Epple, G., Stich, J., Zaba, M., & Schmidt, U. (2017) · BMC Medicine · doi:10.1186/s12916-017-0801-0 · Cited by 57 · see citing works
Oxytocin and vasopressin inhibit hyper-aggressive behaviour in socially isolated mice
Tan, O., Musullulu, H., Raymond, J. S., Wilson, B. B., Langguth, M., & Bowen, M. T. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.03.016 · Cited by 56 · see citing works
Putnam, P. T., Roman, J. M., Zimmerman, P. E., & Gothard, K. M. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.05.016 · Cited by 53 · see citing works
“Although IN-OT does increase the CSF levels of OT (Dal Monte et al., 2014b; Modi et al., 2014) we also cannot rule out the possibility that the observed results are due, at least in part, to the peripheral effects of OT (Leng and Ludwig, 2015).”
Yao, S., & Kendrick, K. M. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14020323 · Cited by 52 · see citing works
Oppong‐Damoah, A., Zaman, R. U., D’Souza, M. J., & Murnane, K. S. (2018) · Hormones and Behavior · doi:10.1016/j.yhbeh.2018.12.011 · Cited by 49 · see citing works
The two fold role of oxytocin in social developmental disorders: A cause and a remedy?
Lefèvre, A., & Angela Sirigu, B. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.01.011 · Cited by 45 · see citing works
Oxytocin regulates reunion affiliation with a pairmate following social separation in marmosets
Cavanaugh, J., Mustoe, A. C., & French, J. A. (2018) · American Journal of Primatology · doi:10.1002/ajp.22750 · Cited by 41 · see citing works
Oxytocin Receptor Signaling in Vascular Function and Stroke
McKay, E. C., & Counts, S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.574499 · Cited by 41 · 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
Self-citationIntranasal Oxytocin and Vasopressin Modulate Divergent Brainwide Functional Substrates
Galbusera, A., Felice, A. D., Girardi, S., Bassetto, G., Maschietto, M., Nishimori, K., Chini, B., Papaleo, F., Vassanelli, S., & Gozzi, A. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.283 · Cited by 38 · see citing works
Alaerts, K., Bernaerts, S., Vanaudenaerde, B. M., Daniëls, N., & Wenderoth, N. (2019) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2019.01.008 · Cited by 40 · see citing works
Marmosets treated with oxytocin are more socially attractive to their long-term mate
Cavanaugh, J., Huffman, M. C., Harnisch, A. M., & French, J. A. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00251 · Cited by 36 · see citing works
McCormack, S. E., Wang, Z., Wade, K., Dedio, A., Cilenti, N. A., Crowley, J., Plessow, F., Bamba, V., Roizen, J. D., Jiang, Y., et al. (2023) · Journal of the Endocrine Society · doi:10.1210/jendso/bvad037 · Cited by 33 · see citing works
Oxytocin and potential benefits for obesity treatment
Olszewski, P. K., Klockars, A., & Levine, A. S. (2017) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000351 · Cited by 37 · see citing works
Kou, J., Lan, C., Zhang, Y., Wang, Q., Zhou, F., Zhao, Z., Montag, C., Yao, S., Becker, B., & Kendrick, K. M. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01241-w · Cited by 37 · see citing works
Simpson, E. A., Paukner, A., Sclafani, V., Kaburu, S., Suomi, S. J., & Ferrari, P. F. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4480-x · Cited by 36 · see citing works
The Potential of Nasal Oxytocin Administration for Remediation of Autism Spectrum Disorders
Okamoto, Y., Ishitobi, M., Wada, Y., & Kosaka, H. (2016) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527315666160413120845 · Cited by 33 · see citing works
Xu, X., Yao, S., Xu, L., Geng, Y., Zhao, W., Ma, X., Kou, J., Luo, R., & Kendrick, K. M. (2017) · Scientific Reports · doi:10.1038/srep40589 · Cited by 33 · see citing works
Oxytocin and Facial Emotion Recognition
Ellenbogen, M. A. (2017) · Current topics in behavioral neurosciences · doi:10.1007/7854_2017_20 · Cited by 33 · see citing works
Oxytocin and interpersonal relationships
Patin, A., Scheele, D., & Hurlemann, R. (2017) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2017_22 · Cited by 32 · see citing works
The Neuropeptide Oxytocin Enhances Information Sharing and Group Decision Making Quality
de Wilde, T. R. W., Velden, F. S. T., & Dreu, C. K. W. D. (2017) · Scientific Reports · doi:10.1038/srep40622 · Cited by 30 · see citing works
Oxytocin Fails to Recruit Serotonergic Neurotransmission in the Autistic Brain
Lefèvre, A., Mottolese, R., Redouté, J., Costes, N., Bars, D. L., Geoffray, M., Leboyer, M., & Angela Sirigu, B. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx272 · 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
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 · see citing works
Oxytocin as an Anti-obesity Treatment
Niu, J., Tong, J., & Blevins, J. E. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.743546 · Cited by 30 · see citing works
Wiśniewski, K. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9504-2_11 · Cited by 28 · see citing works
Kelly, A. M., & Ophir, A. G. (2015) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2015.10.010 · Cited by 28 · see citing works
Divergent effects of oxytocin on eye contact in bonobos and chimpanzees
Brooks, J., Kano, F., Sato, Y., Yeow, H., Morimura, N., Nagasawa, M., Kikusui, T., & Yamamoto, S. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.105119 · Cited by 27 · see citing works
Althaus, M., Groen, Y., Wijers, A. A., Noltes, H., Tucha, O. M., Sweep, F. C. G. J., Calcagnoli, F., & Hoekstra, P. J. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4339-1 · Cited by 27 · see citing works
Fifty Years of Advances in Neuroendocrinology
Russell, J. A. (2018) · Brain and Neuroscience Advances · doi:10.1177/2398212818812014 · Cited by 26 · see citing works
Moy, S. S., Teng, B. L., Nikolova, V. D., Riddick, N. V., Simpson, C. D., Deusen, A. L. V., Janzen, W. P., Sassano, M. F., Pedersen, C. A., & Jarstfer, M. B. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.10.036 · Cited by 26 · see citing works
Opportunities and challenges for intranasal oxytocin treatment studies in nonhuman primates
Bauman, M. D., Murai, T., Hogrefe, C. E., & Platt, M. L. (2018) · American Journal of Primatology · doi:10.1002/ajp.22913 · Cited by 25 · see citing works
Río, R. T.-D., van den Burg, E. H., Stoop, R., & Hegoburu, C. (2018) · Psychopharmacology · doi:10.1007/s00213-018-5030-5 · Cited by 25 · see citing works
Measuring peripheral oxytocin and vasopressin in nonhuman primates
Ziegler, T. E. (2018) · American Journal of Primatology · doi:10.1002/ajp.22871 · Cited by 24 · see citing works
Intranasal oxytocin enhances socially-reinforced learning in rhesus monkeys
Parr, L. A. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00278 · Cited by 23 · see citing works
Hall, K., Smith, M. F., Russell, J. L., Lambeth, S. P., Schapiro, S. J., & Brosnan, S. F. (2019) · Animal Behavior and Cognition · doi:10.26451/abc.06.01.04.2019 · Cited by 23 · see citing works
Effects of chronic oxytocin on attention to dynamic facial expressions in infant macaques
Parr, L. A., Brooks, J. M., Jonesteller, T., Moss, S., Jordano, J. O., & Heitz, T. R. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.08.028 · Cited by 23 · see citing works
Oxytocin improves the ability of dogs to follow informative pointing: a neuroemotional hypothesis
Macchitella, L., Stegagno, T., Giaconella, R., di Sorrentino, E. P., Schino, G., & Addessi, E. (2016) · RENDICONTI LINCEI · doi:10.1007/s12210-016-0579-6 · Cited by 22 · see citing works
Bowen, M. T. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104325 · Cited by 22 · see citing works
Oxytocin and vasopressin increase male-directed threats and vocalizations in female macaques
Jiang, Y., & Platt, M. L. (2018) · Scientific Reports · doi:10.1038/s41598-018-36332-0 · Cited by 19 · see citing works
Díaz‐Marsá, M., López‐Villatoro, J. M., de la Torre‐Luque, A., MacDowell, K. S., Gálvez-Merlín, A., del Barrio, A. G., Ruiz-Guerrero, F., Beato‐Fernández, L., Polo, F., León-Velasco, M., et al. (2023) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2023.12.032 · Cited by 19 · see citing works
Busnelli, M., Dagani, J., de Girolamo, G., Balestrieri, M., Pini, S., Saviotti, F. M., Scocco, P., Sisti, D., Rocchi, M., & Chini, B. (2015) · Journal of Neuroendocrinology · doi:10.1111/jne.12359 · Cited by 18 · see citing works
Increased Serum and Urinary Oxytocin Concentrations after Nasal Administration in Beagle Dogs
Temesi, A., Thuróczy, J., Balogh, L., & Miklósi, Á. (2017) · Frontiers in Veterinary Science · doi:10.3389/fvets.2017.00147 · Cited by 18 · see citing works
Madrid, J. E., Oztan, O., Sclafani, V., Rosso, L. A. D., Calonder, L. A., Chun, K., Capitanio, J. P., Garner, J. P., & Parker, K. J. (2017) · Scientific Reports · doi:10.1038/s41598-017-13109-5 · Cited by 17 · see citing works
Sedative Effects of Intranasal Oxytocin in Rabbits and Rhesus Monkeys
HESS, L., Votava, M., Málek, J., Kurzová, A., & Slíva, J. (2016) · Physiological Research · doi:10.33549/physiolres.933513 · Cited by 17 · see citing works
Gulevich, R., Kozhemyakina, R., Shikhevich, S., Konoshenko, M., & Herbeck, Y. (2019) · Physiology & Behavior · doi:10.1016/j.physbeh.2018.11.030 · Cited by 16 · see citing works
Smith, M. F., Leverett, K. L., Wilson, B. J., & Brosnan, S. F. (2019) · American Journal of Primatology · doi:10.1002/ajp.22973 · Cited by 16 · see citing works
Zarei, S. A., Sheibani, V., Tomaz, C. A. B., & Mansouri, F. A. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.12.050 · Cited by 16 · see citing works
Taubert, J., Flessert, M., Liu, N., & Ungerleider, L. G. (2019) · Scientific Reports · doi:10.1038/s41598-019-51422-3 · Cited by 16 · see citing works
Imaging neuropeptide effects on human brain function
Lefèvre, A., Hurlemann, R., & Grinevich, V. (2018) · Cell and Tissue Research · doi:10.1007/s00441-018-2899-6 · Cited by 16 · see citing works
Intranasal Oxytocin Failed to Affect Chimpanzee (Pan troglodytes) Social Behavior
Proctor, D. P., Calcutt, S. E., Burke, K., & de Waal, F. Β. Μ. (2016) · Animal Behavior and Cognition · doi:10.12966/abc.04.08.2016 · Cited by 14 · see citing works
Intranasal Oxytocin Does Not Modulate Responses to Alcohol in Social Drinkers
Vena, A. A., King, A. C., Lee, R., & de Wit, H. (2018) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13814 · Cited by 14 · see citing works
Intranasal oxytocin in rhesus monkeys alters brain networks that detect social salience and reward
Parr, L. A., Mitchell, T., & Hecht, E. E. (2018) · American Journal of Primatology · doi:10.1002/ajp.22915 · Cited by 13 · see citing works
- Authors
- Modi, M. E., Connor-Stroud, F., Landgraf, R., Young, L. J., & Parr, L. A.
- Affiliations
- Emory University (US)
- Max Planck Institute of Psychiatry (DE)
- Corresponding author
- Modi, Meera E.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 45
- Pages
- 49-57
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC4120060
- OpenAlex
- W2043628043
- Cited by
- 129
- References
- 53
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 16 · 2018: 23 · 2017: 18 · 2016: 24 · 2015: 15 · 2014: 9 · 2013: 1
- FWCI
- 32.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Science Foundation
- Emory University
- National Institutes of Health (P51OD011132)
- Yerkes National Primate Research Center, Emory University
- National Institute of Mental Health (K02MH064692, MH064692, MH068791, R21MH090776, R01MH068791, P50MH100023)
- National Center for Research Resources (P51RR165, P51RR000165)
- Office of Research Infrastructure Programs, National Institutes of Health
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, rhesus monkeys, intranasal administration, intravenous administration, vasopressin, route of administration, social cognition, autism spectrum disorder, pharmacotherapy
- MeSH terms
- Administration, Intranasal, Aerosols, Animals, Biological Availability, Macaca mulatta, Male, Oxytocin, Time Factors, Up-Regulation, Nasal Sprays, Administration, Intravenous
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
