The DOI matches its Crossref record; 72 of the 73 references it cites were found in a registry or an index.
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
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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
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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