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The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta)
Open accessAbstract
The rhesus macaque (Macaca mulatta) is an important primate model for social cognition, and recent studies have begun to explore the impact of oxytocin on social cognition and behavior. Macaques have great potential for elucidating the neural mechanisms by which oxytocin modulates social cognition, which has implications for oxytocin-based pharmacotherapies for psychiatric disorders such as autism and schizophrenia. Previous attempts to localize oxytocin receptors (OXTR) in the rhesus macaque brain have failed due to reduced selectivity of radioligands, which in primates bind to both OXTR and the structurally similar vasopressin 1a receptor (AVPR1A). We have developed a pharmacologically-informed competitive binding autoradiography protocol that selectively reveals OXTR and AVPR1A binding sites in primate brain sections. Using this protocol, we describe the neuroanatomical distribution of OXTR in the macaque. Finally, we use in situ hybridization to localize OXTR mRNA. Our results demonstrate that OXTR expression in the macaque brain is much more restricted than AVPR1A. OXTR is largely limited to the nucleus basalis of Meynert, pedunculopontine tegmental nucleus, the superficial gray layer of the superior colliculus, the trapezoid body, and the ventromedial hypothalamus. These regions are involved in a variety of functions relevant to social cognition, including modulating visual attention, processing auditory and multimodal sensory stimuli, and controlling orienting responses to visual stimuli. These results provide insights into the neural mechanisms by which oxytocin modulates social cognition and behavior in this species, which, like humans, uses vision and audition as the primary modalities for social communication.
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In the citing paper
“OT receptors are concentrated in cholinergic brain regions regulating visual and auditory attention in nonhuman primates (6, 42, 43)”
From Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies (2016) · cites this paper as [42]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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 [99]
In the citing paper
“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 [37]
In the citing paper
“These radioligands are now known to bind to both receptor types when they are used in primate brain37.”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [37]
In the citing paper
“Although these compounds bind selectively to their respective receptors in rodents, they have now been shown to exhibit relatively high affinities for both OXTR and AVPR1a in primates (27,28).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [27]
In the citing paper
“With this method, which combines the use of the radioligands mentioned above with selective competitor ligands, we have now successfully mapped OXTR in the brain of the most common NHP model organism used in biomedical research: the rhesus macaque (Macaca mulatta) (27).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [27]
In the citing paper
“We have recently reported the design of a pharmacologically optimised method for competitive binding receptor autoradiography that can selectively and reliably reveal the distributions of OXTR and AVPR1a in primate tissue (27).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [27]
In the citing paper
“The rhesus macaque brain in general exhibits extremely sparse OXTR expression relative to AVPR1a (27,31), with the most dense OXTR binding seen in the NBM and superficial grey layer of the SC (Fig. 2c,f).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [27]
In the citing paper
“ALS-II-69 was evaluated in previous studies and shown to effectively block OXTR radioligand binding to primate brain tissue (27).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [27]
In the citing paper
“However, we now know that this region of the macaque brain does not contain detectable levels of OXTR binding (27), although OXTR may be present on NBM terminals in the amygdala.”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [27]
In the citing paper
“OXTR is distributed throughout the brain of many vertebrates and, importantly, the pattern of OXTR distribution is diverse between species (32, 33).”
From Variation in the Oxytocin Receptor Gene Predicts Brain Region–Specific Expression and Social Attachment (2016) · cites this paper as [33]
In the citing paper
“In primates, OTR has been detected in the superior colliculus, the pulvinar, and the primary visual cortex (Freeman et al. 2014).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Freeman et al. 2014
In the citing paper
“There is a high density of OT receptors in the amygdala (Insel and Shapiro, 1992; but see Freeman et al., 2014).”
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 Freeman et al., 2014
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Citations
Cites
Massagué, J. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.753 · Cited by 7,571
The neurobiology of pair bonding.
Young, L. J., & Wang, Z. (2004) · Nature Neuroscience · doi:10.1038/nn1327 · Cited by 1,523 · cited 1×
“The neuroanatomical localization of OXTR using receptor autoradiography has been useful for identifying neural mechanisms of OT action in rodents (Ferguson et al., 2001; Young and Wang, 2004).”
MethodKnobil and Neill's Physiology of Reproduction
(2015) · Elsevier eBooks · doi:10.1016/c2011-1-07288-0 · Cited by 1,277
Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin
Dölen, G., Darvishzadeh, A., Huang, K. W., & Malenka, R. C. (2013) · Nature · doi:10.1038/nature12518 · Cited by 1,161
The Rhesus Monkey Brain in Stereotaxic Coordinates
Paxinos, G., Huang, X., & Toga, A. W. (1999) · Research Online (University of Wollongong) · Cited by 1,070
Oxytocin in the Medial Amygdala is Essential for Social Recognition in the Mouse
Ferguson, J. N., Aldag, J. M., Insel, T. R., & Young, L. J. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-20-08278.2001 · Cited by 1,043 · cited 4×
“The neuroanatomical localization of OXTR using receptor autoradiography has been useful for identifying neural mechanisms of OT action in rodents (Ferguson et al., 2001; Young and Wang, 2004).”
BackgroundMethodInfluentialPromoting 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 · cited 1×
“The OT system is a potential target for enhancing social cognition in psychiatric disorders (Modi and Young, 2012), and several studies have now shown that IN-OT improves some aspects of social functioning in autism spectrum disorder (Andari et al., 2010; Domes et al., 2013; Hollander et al., 2007).”
BackgroundOxytocin 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 · cited 1×
“The OT system is a potential target for enhancing social cognition in psychiatric disorders (Modi and Young, 2012), and several studies have now shown that IN-OT improves some aspects of social functioning in autism spectrum disorder (Andari et al., 2010; Domes et al., 2013; Hollander et al., 2007).”
BackgroundLim, M. M., Wang, Z., Olazábal, D. E., Ren, X., Terwilliger, E. F., & Young, L. J. (2004) · Nature · doi:10.1038/nature02539 · Cited by 628 · cited 2×
“…vector gene manipulations, and transgenic mouse technology have led to the elucidation of the neural mechanisms underlying the effects of these neuropeptides and their receptors on these complex social behaviors (Dölen et al., 2013; Ferguson et al., 2001; Lim et al., 2004b; Owen et al., 2013).”
BackgroundMethodSelf-citationYoshida, M., Takayanagi, Y., Inoue, K., Kimura, T., Young, L. J., Onaka, T., & Nishimori, K. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5593-08.2009 · Cited by 608 · cited 2×
“However using IHC to stain for OXTR has been notoriously problematic; a study that tested six different OXTR antibodies found that all of them produced identical patterns of staining in brain tissue from wildtype and OXTR knockout mice, indicating their unreliability in detecting OXTR in rodent brain (Yoshida et al.,…”
Background
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
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
Plasticity of Cortical Excitatory-Inhibitory Balance
Froemke, R. C. (2015) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071714-034002 · Cited by 458
“Oxytocin may be an important modulator of nucleus basalis, as indicated by recent autoradiography and in situ hybridization data from macaques (Freeman et al. 2014).”
BackgroundOxytocin enhances social recognition by modulating cortical control of early olfactory processing
Oettl, L.-L., Ravi, N., Schneider, M., Scheller, M. F., Schneider, P., Mitre, M., da Silva Gouveia, M., Froemke, R. C., Chao, M. V., Young, W. S., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.03.033 · Cited by 359
“…and early cortical visual areas and cholinergic nuclei controlling sensory processing in these modalities, suggesting the involvement of OXT in a variety of functions relevant to social cognition, including modulating visual attention, processing, and sensory stimuli (Freeman et al., 2014a, 2014b).”
Environmental influence in the brain, human welfare and mental health
Tost, H., Champagne, F. A., & Meyer‐Lindenberg, A. (2015) · Nature Neuroscience · doi:10.1038/nn.4108 · Cited by 370
Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies
Walum, H., Waldman, I. D., & Young, L. J. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.06.016 · Cited by 347
“For example, OT receptors are concentrated in cholinergic brain regions regulating visual and auditory attention in nonhuman primates (6, 42, 43), consistent with the putative localization of OT receptors in human brain (44).”
BackgroundAssembling the puzzle: pathways of oxytocin signaling in the brain
Grinevich, V., Knobloch-Bollmann, H. S., Eliava, M., Busnelli, M., & Chini, B. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.04.013 · Cited by 309
“supports the hypothesis that, in primates, OTRs act at the most relevant sensory modalities to regulate social approach and behavior (29) (Figure 4).”
BackgroundJohnson, Z. V., & Young, L. J. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.01.034 · Cited by 242
“exhibit dense OTR expression in the NAc, while socially monogamous and alloparental coppery titi monkeys exhibit dense V1aR expression in this region (Freeman and Young, 2016); in contrast, non-monogamous rhesus macaques exhibit low levels of OTR and V1aR binding in the NAc (Figure 2) (Freeman et al., 2014; Young et a…”
Prefrontal–amygdala circuits in social decision-making
Gangopadhyay, P., Chawla, M., Monte, O. D., & Chang, S. W. C. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-00738-9 · Cited by 266
Baribeau, D. A., & Anagnostou, E. A. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00335 · Cited by 241
“Oxytocin has a single receptor (OXTR) encoded on chromosome 3, whereas vasopressin has three types of receptors, AVPR1a and AVPR1b (also called V3) and V2, on chromosome 20 (De Keyzer et al., 1994; Thibonnier et al., 2002).”
BackgroundInfluentialGenetic origins of social networks in rhesus macaques
Brent, L. J. N., Heilbronner, S. R., Horvath, J. E., Gonzalez-Martinez, J., Ruiz-Lambides, A., Robinson, A. G., Skene, J. H. P., & Platt, M. L. (2013) · Scientific Reports · doi:10.1038/srep01042 · Cited by 220
Freeman, S. M., & Young, L. J. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12382 · Cited by 196
“ALS-II-69 was evaluated in previous studies and shown to effectively block OXTR radioligand binding to primate brain tissue (27).”
BackgroundMethodInfluentialKing, L. B., Walum, H., Inoue, K., Eyrich, N. W., & Young, L. J. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.12.008 · Cited by 191
“The OXTR is distributed throughout the brain of many vertebrates, and the pattern of OXTR distribution is diverse among species (32,33).”
Young, L. J., & Barrett, C. E. (2015) · Science · doi:10.1126/science.aaa8120 · Cited by 200
Self-citationYamasue, H., Okada, T., Munesue, T., Kuroda, M., Fujioka, T., Uno, Y., Matsumoto, K., Kuwabara, H., Mori, D., Okamoto, Y., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-018-0097-2 · Cited by 185
Hormonal influences in migraine — interactions of oestrogen, oxytocin and CGRP
Krause, D. N., Warfvinge, K., Haanes, K. A., & Edvinsson, L. I. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00544-2 · Cited by 214
Blevins, J. E., Graham, J. L., Morton, G. J., Bales, K. L., Schwartz, M. W., Baskin, D. G., & Havel, P. J. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00441.2014 · Cited by 191
“While systemic OT increases the induction of Fos (a marker of neuronal activation) in the VMH in mice (72) and OTRs are expressed in the VMH of rhesus monkeys (9, 24), it remains to be determined whether systemic OT is capable of reaching OTRs in the DMH or VMH in sufficient concentrations to stimulate EE in rhesus mo…”
Parker, K. J., Oztan, O., Libove, R. A., Mohsin, N., Karhson, D. S., Sumiyoshi, R. D., Summers, J. E., Hinman, K. E., Motonaga, K. S., Phillips, J. M., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aau7356 · Cited by 185
Klin, A., Shultz, S., & JONES, W. R. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.10.006 · Cited by 204
Neurobiological mechanisms of social attachment and pair bonding
Johnson, Z. V., & Young, L. J. (2015) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2015.01.009 · Cited by 169
Self-citationNeural mechanisms of social decision-making in the primate amygdala
Chang, S. W. C., Fagan, N. A., Toda, K., Utevsky, A. V., Pearson, J. M., & Platt, M. L. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1514761112 · Cited by 157
“Recently, it has been demonstrated that OT administration modulates hemodynamic activity in the amygdala in rhesus macaques (30), and it has been hypothesized that the primate amygdala may express presynaptic OT receptors (46).”
BackgroundFreeman, 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
“In the rhesus macaque, OXTR distribution is even further restricted, with low levels of expression detectable in only five areas of the brain: NBM, ventromedial hypothalamus (VMH), SuG, trapezoid body (TB), and the pedunculopontine tegmental nucleus (PPT)(Freeman et al., in press).”
BackgroundMethodResultInfluentialOxytocin and the Neurobiology of Prosocial Behavior
Marsh, N., Marsh, A. A., Lee, M. R., & Hurlemann, R. (2020) · The Neuroscientist · doi:10.1177/1073858420960111 · Cited by 159
Oxytocin and Pain Perception: From Animal Models to Human Research
Boll, S., de Minas, A. C. A., Raftogianni, A., Herpertz, S. C., & Grinevich, V. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.09.041 · Cited by 141
Blevins, J. E., & Baskin, D. G. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.05.023 · Cited by 135
“nucleus accumbens, preoptic area, VMH, DMV, and spinal cord) [73–75] and humans (e.”
BackgroundLabeled 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
Aerosolized oxytocin increases cerebrospinal fluid oxytocin in rhesus macaques
Modi, M. E., Connor-Stroud, F., Landgraf, R., Young, L. J., & Parr, L. A. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.02.011 · Cited by 129
“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).”
Oxytocin in the socioemotional brain: implications for psychiatric disorders
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Oxytocin and social functioning
Jones, C., Barrera, I., Brothers, S., Ring, R., & Wahlestedt, C. (2017) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2017.19.2/cjones · Cited by 132
Oxytocin receptors modulate a social salience neural network in male prairie voles
Johnson, Z. V., Walum, H., Xiao, Y., Riefkohl, P. C., & Young, L. J. (2017) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.10.009 · Cited by 113
Oxytocin reduces alcohol cue-reactivity in alcohol-dependent rats and humans
Hansson, A. C., Koopmann, A., Uhrig, S., Bühler, S., Domi, E., Kiessling, E., Ciccocioppo, R., Froemke, R. C., Grinevich, V., Kiefer, F., et al. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.257 · Cited by 109
“However, some studies on non-human primates suggest significant binding to other nonapeptide receptors, most notably vasopressin 1a receptors (Toloczko et al, 1997; Freeman et al, 2014a, b).”
BackgroundMethodA Review of Oxytocin’s Effects on the Positive, Negative, and Cognitive Domains of Schizophrenia
Feifel, D., Shilling, P. D., & MacDonald, K. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.07.025 · Cited by 110
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 116
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
Cataldo, I., Azhari, A., & Esposito, G. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00027 · Cited by 97
“…et al., 2015; Wang et al., 2016), processing and recognition of facial expressions (Israel et al., 2008; Knafo et al., 2008; Moons et al., 2014; Uzefovsky et al., 2015; Wang et al., 2016) and non-human mammals (Murakami et al., 2011; Freeman et al., 2014; Paré et al., 2016; Lesse et al., 2017).”
BackgroundLin, Y.-T., & Hsu, K. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.10.003 · Cited by 102
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 100
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
Leng, G., & Sabatier, N. (2017) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2017.02.007 · Cited by 90
Adaptations for social cognition in the primate brain
Platt, M. L., Seyfarth, R. M., & Cheney, D. L. (2016) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2015.0096 · Cited by 95
“Recent studies have demonstrated that OT receptors in both monogamous titi monkeys (Callicebus cupreus) and rhesus macaques [127,128] appear to be limited to areas of the hypothalamus and brainstem implicated in arousal and visual orienting behaviour.”
BackgroundOxytocin receptor dynamics in the brain across development and species
Vaidyanathan, R., & Hammock, E. A. D. (2016) · Developmental Neurobiology · doi:10.1002/dneu.22403 · Cited by 86
“…well demonstrated within the brain (Insel et al., 1991; Dubois-Dauphin et al., 1992; Insel and Shapiro, 1992; Insel et al., 1993; Young et al., 1996; Wang and Young, 1997; Rabhi et al., 1999; Olazabal and Young, 2006; Beery et al., 2008; Campbell et al., 2009; Freeman et al., 2014a, 2014b).”
BackgroundKrol, K. M., Puglia, M. H., Morris, J. P., Connelly, J. J., & Grossmann, T. (2019) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2019.100648 · Cited by 86
“Limited work in the non-human primate brain reports the majority of OXTR in subcortical regions (Freeman et al., 2014a, b; Freeman and Young, 2016).”
Bürkner, P., Williams, D. R., Simmons, T. C., & Woolley, J. D. (2017) · Schizophrenia Bulletin · doi:10.1093/schbul/sbx053 · Cited by 82
Uhrig, S., Hirth, N., Broccoli, L., von Wilmsdorff, M., Bauer, M., Sommer, C., Zink, M., Steiner, J. H., Frodl, T., Malchow, B., et al. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.04.019 · Cited by 73
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Bauman, M. D., & Schumann, C. M. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.07.021 · Cited by 74
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Carson, D. S., Garner, J. P., Hyde, S. A., Libove, R. A., Berquist, S. W., Hornbeak, K. B., Jackson, L. P., Sumiyoshi, R. D., Howerton, C. L., Hannah, S. L., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0132224 · Cited by 71
Oxytocin and Serotonin Brain Mechanisms in the Nonhuman Primate
Lefèvre, A., Richard, N., Jazayeri, M., Beuriat, P.-A., Fieux, S., Zimmer, L., Duhamel, J., & Sirigu, A. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.0659-17.2017 · Cited by 73
“…in the primate brain is not well understood; and although they have not been found in limbic areas of humans and macaques (Loup et al., 1991; Freeman et al., 2014; but see Boccia et al., 2013), administration of OT has consistently produced effects in these areas (Chang et al., 2015;…”
BackgroundTabak, B. A., Meyer, M. L., Castle, E., Dutcher, J. M., Irwin, M. R., Han, J. H., Lieberman, M. D., & Eisenberger, N. I. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.10.006 · Cited by 67
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
“…968in the visual processing areas in primates is consistent with the 969importance and predominance of visual stimuli in primate social 970relationships, akin to the central role of olfaction, and the rich 971expression of OTR in odor-processing networks, in rodents 972(Freeman et al., 2014b).”
InfluentialOxytocin 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
“In the rhesus monkey brain, OT receptors are most robustly expressed in the nucleus basalis of Meynert, the superficial gray layer of the superior colliculus, the pedunculopontine tegmental nucleus, the trapezoid body, and the ventromedial hypothalamus (37).”
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Fagan, H. A., & Baldwin, D. S. (2023) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2023.2211767 · Cited by 82
“widely throughout the mammalian brain [120].”
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Oxytocin, social cognition and psychiatry
Young, L. J. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2014.186 · Cited by 64
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 67
“…direct approach to modulate oxytocinergic signaling is through activation of the OT receptor (OXTR), a class-A G-protein-coupled receptor (GPCR) expressed throughout the central nervous system (CNS) and in several peripheral tissues, including the uterus, mammary glands, heart, and kidney [16,17].”
Adaptive coding of the value of social cues with oxytocin, an fMRI study in autism spectrum disorder
Andari, E., Richard, N., Leboyer, M., & Sirigu, A. (2016) · Cortex · doi:10.1016/j.cortex.2015.12.010 · Cited by 62
Titi Monkeys as a Novel Non-Human Primate Model for the Neurobiology of Pair Bonding .
Bales, K. L., Razo, R. A., Conklin, Q. A., Hartman, S., Mayer, H. S., Rogers, F. D., Simmons, T. C., Smith, L. K., Williams, A. V., Williams, D. R., et al. (2017) · Europe PMC (PubMed Central) · Cited by 62
The Role of Hypothalamic Neuropeptides in Neurogenesis and Neuritogenesis
Bakoš, J., Zatkova, M., Bačová, Z., & Ostatníková, D. (2016) · Neural Plasticity · doi:10.1155/2016/3276383 · Cited by 63
“Neural circuitry for social cognition depends on oxytocin and vasopressin receptor density in specific brain regions [119, 120].”
BackgroundThe Neurobiology of Love and Pair Bonding from Human and Animal Perspectives
Blumenthal, S. A., & Young, L. J. (2023) · Biology · doi:10.3390/biology12060844 · Cited by 59
“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].”
BackgroundModulation of social behavior by distinct vasopressin sources
Rigney, N., Vries, G. J. D., & Petrulis, A. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1127792 · Cited by 64
Ebert, A., & Brüne, M. (2017) · Current topics in behavioral neurosciences · doi:10.1007/7854_2017_21 · Cited by 66
Marmosets as model species in neuroscience and evolutionary anthropology
Burkart, J. M., & Finkenwirth, C. (2014) · Neuroscience Research · doi:10.1016/j.neures.2014.09.003 · Cited by 63
Translating Oxytocin Neuroscience to the Clinic: A National Institute of Mental Health Perspective
Insel, T. R. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.02.002 · Cited by 56
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
“including the nucleus basalis of Meynert (NBM) (Freeman et al., 2014).”
Circuits for social learning: a unified model and application to autism spectrum disorder
DeMayo, M. M., Young, L. J., Hickie, I. B., Song, Y. J. C., & Guastella, A. J. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.09.034 · Cited by 52
Duque‐Wilckens, N., Steinman, M. Q., Laredo, S. A., Hao, R., Perkeybile, A. M., Bales, K. L., & Trainor, B. C. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.07.018 · Cited by 54
“…in V1aR binding (Bester-Meredith et al., 1999; Hammock and Young, 2006), dense V1aR binding in the bed nucleus of the stria terminalis (BNST) is observed in a diverse group of rodents (Bales et al., 2007; Bosch et al., 2010) and primates (Freeman et al., 2014a, 2014b; Young et al., 1999).”
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
“The slides were processed for OXTR receptor autoradiography as described previously (Freeman et al., 2014a).”
BackgroundMethodResultInfluentialDevelopmental effects of oxytocin neurons on social affiliation and processing of social information
Nunes, A. R., Gliksberg, M., Varela, S. A. M., Teles, M., Wircer, E., Blechman, J., Petri, G., Levkowitz, G., & Oliveira, R. F. (2021) · The Journal of Neuroscience · doi:10.1523/jneurosci.2939-20.2021 · Cited by 47
Association between the oxytocin receptor ( OXTR ) gene and children's social cognition at 18 months
Wade, M., Hoffmann, T. J., Wigg, K., & Jenkins, J. M. (2014) · Genes Brain & Behavior · doi:10.1111/gbb.12148 · Cited by 55
“Interestingly, OXTR has been found in non-human species to be distributed in several brain regions known to support social cognition (Freeman et al. 2014; Vaccari et al. 1998).”
Inoue, K., Ford, C. L., Horie, K., & Young, L. J. (2022) · Journal of Comparative Neurology · doi:10.1002/cne.25382 · Cited by 45
“In primates, OXTRs are more densely expressed in areas responsible for visual information processing and attention, including the nucleus basalis of Meynert and superior colliculus (S. M. Freeman et al., 2014; S. M. Freeman & Young, 2016; Grebe et al., 2021).”
BackgroundSelf-citationKranz, T. M., Kopp, M., Waltes, R., Sachse, M., Duketis, E., Jarczok, T. A., Degenhardt, F., Görgen, K., Meyer, J., Freitag, C. M., et al. (2016) · Autism Research · doi:10.1002/aur.1597 · Cited by 47
“…processing social cues like the olfactory bulb and the medial amygdala, rhesus macaques show the highest OXTR levels in cholinergic brain regions such as the nucleus basalis of Meynert (NBM), which sends massive projections to the limbic brain system and the neocortex [Freeman et al., 2014].”
BackgroundNeuropeptide Regulation of Social Attachment: The Prairie Vole Model
Tabbaa, M., Paedae, B., Liu, Y., & Wang, Z. (2016) · Comprehensive physiology · doi:10.1002/cphy.c150055 · Cited by 53
“MPOA, medial preoptic area of the hypothalamus; NAcc, nucleus accumbens; OB, olfactory bulb; PFC, prefrontal cortex; Pit, pituitary gland; SON, supraoptic nucleus; VMH, ventromedial hypothalamus; VP, ventral pallidum; VTA, ventral tegmental area.”
InfluentialIntranasal gene delivery for treating Parkinson’s disease: overcoming the blood–brain barrier
Aly, A. E.-E., & Waszczak, B. L. (2015) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2015.1069815 · Cited by 46
“Oxytocin receptor expression is very restricted in the brain, with most expression in areas related to visual processing, sensory functions and social cognition [59].”
BackgroundLee, M. R., Sheskier, M. B., Farokhnia, M., Feng, N., Marenco, S., Lipska, B. K., & Leggio, L. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.05.039 · Cited by 44
Oxytocin and Anxiety Disorders: Translational and Therapeutic Aspects
Naja, W., & Aoun, M. P. (2017) · Current Psychiatry Reports · doi:10.1007/s11920-017-0819-1 · Cited by 42
Positive reinforcing effect of oxytocin microinjection in the rat central nucleus of amygdala
László, K., Kovács, A., Zagorácz, O., Ollmann, T., Péczely, L., Kertes, E., Lacy, D. G., & Lénárd, L. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.09.021 · Cited by 43
An integrated framework for the role of oxytocin in multistage social decision‐making
Piva, M., & Chang, S. W. C. (2018) · American Journal of Primatology · doi:10.1002/ajp.22735 · Cited by 38
“While previous studies were unable to differentiate between OXTRs and vasopressin 1a receptors (AVPR1As), the authors of this study utilized a competitive binding autoradiography protocol that allowed them to specifically localize OXTRs (Freeman et al., 2014).”
BackgroundMethodResultInfluentialA 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
“They are also found in regions involved in attention such as the basal nucleus of Meynert and the diagonal band of Broca that have a high number of cholinergic neurons (Freeman et al. 2014).”
BackgroundSelf-citationThe impact of sex as a biological variable in the search for novel antidepressants
Williams, A. V., & Trainor, B. C. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.05.003 · Cited by 42
Tops, S., Habel, U., & Radke, S. (2018) · Hormones and Behavior · doi:10.1016/j.yhbeh.2018.03.002 · Cited by 42
Prounis, G. S., Thomas, K., & Ophir, A. G. (2018) · The Journal of Comparative Neurology · doi:10.1002/cne.24450 · Cited by 38
“…OTR and V1aR expression in adult rhesus macaques, common marmosets, and copper titi monkeys, and these studies indicate intriguing species differences (Freeman, Inoue, Smith, Goodman, & Young, 2014a; Freeman et al., 2014b; Schorscher-Petcu, Dupre, & Tribollet, 2009; Young, Toloczko, & Insel, 1999).”
BackgroundMarmosets 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
“The OXTA (L368,899r provided by Dr. Peter Williams, Merck and Co., Inc.) is readily absorbed by the bloodstream after passage through the digestive system (Thompson et al., 1997), penetrates the CNS after peripheral administration, and accumulates in areas of the limbic system (Boccia et al., 2007).”
BackgroundSimpson, 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 38
“More recently, researchers have described the neuroanatomical distribution of OT receptors binding and mRNA in rhesus macaques (Freeman et al. 2014).”
BackgroundIntrinsic links among sex, emotion, and reproduction
Yang, L. Y., Comninos, A. N., & Dhillo, W. S. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2802-3 · Cited by 37
“This method of detecting oxytocin and vasopressin binding in humans and non-human primates has since been disputed due to the relative non-specificity and high cross-reactivity of radiolabelled ligands for the oxytocin and vasopressin receptor [128, 129].”
MethodOxytocin increases eye-gaze towards novel social and non-social stimuli
Eckstein, M., Bamert, V., Stephens, S. B. Z., Wallen, K., Young, L. J., Ehlert, U., & Ditzen, B. (2018) · Social Neuroscience · doi:10.1080/17470919.2018.1542341 · Cited by 36
Autism Pathogenesis: The Superior Colliculus
Jure, R. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.01029 · Cited by 38
Kotani, M., Shimono, K., Yoneyama, T., Nakako, T., Matsumoto, K., Ogi, Y., Konoike, N., Nakamura, K., & Ikeda, K. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.05.009 · Cited by 37
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
Oxytocin and Facial Emotion Recognition
Ellenbogen, M. A. (2017) · Current topics in behavioral neurosciences · doi:10.1007/7854_2017_20 · Cited by 34
Johnson, K. V. ‐., & Burnet, P. W. J. (2020) · BMC Neuroscience · doi:10.1186/s12868-020-00583-3 · Cited by 33
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
Oxytocin, vasopressin and social behavior in the age of genome editing: a comparative perspective
Boender, A. J., & Young, L. J. (2020) · Hormones and Behavior · doi:10.1016/j.yhbeh.2020.104780 · Cited by 30
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., & Sirigu, A. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx272 · Cited by 31
García-Boll, E., Martı́nez-Lorenzana, G., Condés‐Lara, M., & González‐Hernández, A. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.11.031 · Cited by 30
“Similar results were obtained in other Primates (Macaca mulatta, Freeman et al., 2014a; Callicebus cupreus, Freeman et al., 2014b).”
ResultBridging 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
Smith, A. L., Freeman, S. M., Barnhart, T. E., Abbott, D. H., Ahlers, E. O., Kukis, D. L., Bales, K. L., Goodman, M. M., & Young, L. J. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.04.097 · Cited by 29
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
Synaptic plasticity as a cortical coding scheme
Froemke, R. C., & Schreiner, C. E. (2015) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.10.003 · Cited by 29
“These systems are also extensively interrelated: in macaques, the cholinergic nucleus basalis expresses a high level of oxytocin receptors [85 ], and a major input to the oxytocin-producing paraventricular nucleus comes from noradrenergic neurons of the brainstem [86].”
BackgroundWade, M., Hoffmann, T. J., & Jenkins, J. M. (2015) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsv064 · Cited by 30
“Studies in non-human primates show that OXTR is selectively distributed in various brain regions known to support social cognition (Freeman et al., 2014).”
BackgroundBAXTER, A. B., Anderson, M., Seelke, A. M. H., Kinnally, E. L., Freeman, S. M., & Bales, K. L. (2020) · Scientific Reports · doi:10.1038/s41598-020-74243-1 · Cited by 26
Maninger, N., Hinde, K., Mendoza, S. P., Mason, W. A., Larke, R. H., Ragen, B., Jarcho, M. R., Cherry, S. R., Rowland, D. J., Ferrer, E. E., et al. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.02.028 · Cited by 27
“In contrast to the more common biomedical model, the rhesus monkey (Macaca mulatta) (Freeman et al., 2014a), titi monkeys display OT receptors in more forebrain areas, including the lateral septum (Freeman et al., 2014b).”
Metadata
- Authors
- Freeman, S. M., Inoue, K., Smith, A. L., Goodman, M. M., & Young, L. J.
- Affiliations
- Emory University (US)
- Corresponding author
- Freeman, Sara M.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 45
- Pages
- 128-141
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC4043226
- OpenAlex
- W1989923863
- Cited by
- 185
- References
- 73
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 7 · 2022: 13 · 2021: 17 · 2020: 9 · 2019: 12 · 2018: 28 · 2017: 26 · 2016: 29 · 2015: 23 · 2014: 10
- FWCI
- 43.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5t32mh073525-05, P51OD011107, P51OD011132)
- National Institute of Mental Health (T32-MH073525, R21MH090776, T32MH073525-06, P50MH100023, MH090776)
- National Center for Research Resources (P51RR000165)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Primate Behavior and Ecology
- Keywords
- oxytocin receptor, vasopressin 1a receptor, AVPR1A, rhesus monkeys, neuroanatomical distribution, nucleus basalis of Meynert, pedunculopontine nucleus, superior colliculus, trapezoid body, ventromedial hypothalamus, social cognition, visual attention, auditory processing, orienting response, autism spectrum disorder, schizophrenia
- MeSH terms
- Animals, Brain, Cricetulus, Cricetinae, Humans, Macaca mulatta, Male, Neurons, Oxytocin, Protein Binding, RNA, Messenger, Tissue Distribution, CHO Cells, Receptors, Oxytocin
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