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Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications
Open accessAbstract
In the last several decades, sophisticated experimental techniques have been used to determine the neurobiology of the oxytocin and vasopressin systems in rodents. Using a suite of methodologies, including electrophysiology, site‐specific selective pharmacology, receptor autoradiography, in vivo microdialysis, and genetic and optogenetic manipulations, we have gained unprecedented knowledge about how these neuropeptides engage neural circuits to regulate behaviour, particularly social behaviour. Based on this foundation of information from rodent studies, we have started generating new hypotheses and frameworks about how the oxytocin and vasopressin systems could be acting in humans to influence social cognition. However, despite the recent inundation of publications using intranasal oxytocin in humans, we still know very little about the neurophysiology of the oxytocin system in primates more broadly. Furthermore, the design and analysis of these human studies have remained largely uninformed of the potential neurobiological mechanisms underlying their findings. Although the methods available for studying the oxytocin and vasopressin systems in humans are incredibly limited as a result of practical and ethical considerations, there is great potential to fill the gaps in our knowledge by developing better nonhuman primate models of social functioning. Behavioural pharmacology and receptor autoradiography have been used to study the oxytocin and vasopressin systems in nonhuman primates, and there is now great potential to broaden our understanding of the neurobiology of these systems. In this review, we discuss comparative findings in receptor distributions in rodents and primates, with perspectives on the functionality of conserved regions of expression in these distinct mammalian clades. We also identify specific ways that established technologies can be used to answer basic research questions in primates. Finally, we highlight areas of future research in nonhuman primates that are experimentally poised to yield critical insights into the anatomy, physiology and behavioural effects of the oxytocin system, given its remarkable translational potential.
Overview
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Written from the paper’s full text.
TL;DR
This review compares oxytocin/vasopressin receptor distributions in rodents and primates, arguing that rodent OXTR is olfactory-centric while primate OXTR is enriched in visual-attention and cholinergic circuits. It concludes that nonhuman primates, guided by selective receptor mapping and pharmacology, can provide mechanistic translational insights that current human intranasal oxytocin studies cannot.
Key findings
- Rodent OXTR expression is concentrated in olfactory pathways (olfactory bulb, accessory olfactory nucleus, medial amygdala, central amygdala, bed nucleus of stria terminalis, piriform cortex) plus lateral septum, hippocampus, NAcc, and prefrontal cortex; primate OXTR overlaps visual processing, gaze, and attention regions (superior colliculus, pulvinar, primary visual cortex, oculomotor nucleus, nucleus prepositus) and cholinergic regions including the nucleus basalis of Meynert in all four species investigated and the pedunculopontine tegmental nucleus in rhesus macaques.
- Species differences are marked: prairie voles have dense NAcc OXTR that is low to absent in meadow and montane voles; marmosets have dense NAcc OXTR; titi monkeys lack NAcc OXTR but have AVPR1a in NAcc and dense OXTR in the dentate gyrus; rhesus macaques show sparse OXTR relative to AVPR1a, with densest OXTR in the NBM and superficial grey layer of the superior colliculus.
- Translational/clinical links include that IN-OT acutely increases gaze to the eye region in autistic populations, three rhesus studies found IN-OT impacts social visual attention and looking behaviours, IN-OT alters neural responses to emotional faces in macaques, and OXTR SNP rs2254298 has been linked to smaller amygdala volume.
- Pharmacological findings: 125I-OVTA and 125I-LVA lose binding selectivity in primate tissue; an optimised competitive binding autoradiography method mapped OXTR in rhesus and titi monkeys; selective antagonists include ALS-II-69, SR49059, and L-368,899, but radiolabelled L-368,899 showed minimal brain uptake and appeared to accumulate in ventricles rather than neural tissue on PET.
Methods
- Design: narrative comparative review of oxytocin and vasopressin receptor research in rodents and primates, with translational implications.
- Data/sample: literature on rodent species (including mice, rats, hamsters, guinea pigs, California and deer mice, tuco-tucos, singing mice, naked and Cape mole-rats, prairie, pine, montane, and meadow voles) and primates (common marmoset, rhesus macaque, coppery titi monkey, human), drawing on receptor autoradiography, behavioural pharmacology, electrophysiology, microdialysis, and genetic/optogenetic manipulations.
- Main analysis: qualitative synthesis of receptor distributions and pharmacological findings; no meta-analysis or new primary quantitative dataset is reported.
Limitations
- The paper states that primate OXTR mapping has lagged because 125I-OVTA and 125I-LVA lose binding selectivity in primate tissue; human OT system methods are “incredibly limited” by practical and ethical considerations; human IN-OT studies are often underpowered with modest effect sizes; and invasive NHP brain manipulations face ethical, cost, and animal welfare constraints.
- The paper states that species differences in receptor distribution mean NHP central OXTR may or may not predict human OXTR, and that IN-OT effects may be mediated by AVPR1a or peripheral OXTR, complicating interpretation.
- Evident from the text: as a narrative review, it relies on selected literature and some unpublished or ongoing observations, without a systematic search or quantitative synthesis.
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Claims the paper makes
72 Not checked yet · 21 Own interpretation · 13 No basis given · 3 Own result · 1 Supported · 1 Partly supported · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Although MC4R agonists show promise for eliciting OT-mediated behaviours, they also interact with other behaviourally relevant neurochemical systems (23) and thus are not useful tools for isolating OT function.”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Implications of knowing OXTR and AVPR1a distributions in NHP > Ligands for behavioural neuropharmacology of the OT system in primates
What the sources say
- Supportedcites [23] Barrett CE Arambula SE Young LJ The oxytocin system promotes resilience to the effects of neonatal isolation on adult social attachment in female prairie voles Transl Psychiatry 2015 5 e606 26196439 PMC5068726 source
The Discussion says MC4R interacts with the dopamine system and activates corticotropin-releasing factor and AVP neurons. It explicitly cautions that the study cannot prove melanocortin-receptor effects on behavior are due to the OT system, supporting the claim that these agonists cannot isolate OT function. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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- Rests on an assumption: A tool must not interact with other behaviourally relevant neurochemical systems to isolate OT function.
- Supported
In the paper
“We have also independently confirmed the findings reported by Schorscher-Petcu et al. (2009) for OXTR and AVPR1a binding in the forebrain of the common marmoset (Callithrix jacchus) (S. M. Freeman, unpublished observations).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > The value and challenges of characterising OXTR and AVPR1a distributions in the brain
What the sources say
- Not checked yetcites Schorscher-Petcu et al. (2009)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the 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).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > The value and challenges of characterising OXTR and AVPR1a distributions in the brain
What the sources say
- Not checked yetcites [27] Freeman SM Inoue K Smith AL Goodman MM Young LJ The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta) Psychoneuroendocrinology 2014 45 128 141 24845184 PMC4043226 source
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“For example, all of the primate species investigated to date have OXTR in the NBM”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Evolutionary perspectives on central OXTR distributions > OXTR in primates is concentrated in brain regions involved in visual processing and attention
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this context, it is not surprising that there is considerable overlap in OXTR expression among primate species in areas that are important for visual processing, shifts in gaze direction and the allocation of attention to visual stimuli (Fig. 1c,d and Table 1).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Evolutionary perspectives on central OXTR distributions > OXTR in primates is concentrated in brain regions involved in visual processing and attention
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In areas involved in saccadic eye movements in response to visual stimuli, OXTR is expressed in the superficial grey layer of the SC (Fig. 2), as well as deeper layers, and in the oculomotor nucleus (III) and the nucleus prepositus, which are two brainstem motor nuclei that control the muscles of the eye and participate in the horizontal gaze stabilisation system, respectively (41-43).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Evolutionary perspectives on central OXTR distributions > OXTR in primates is concentrated in brain regions involved in visual processing and attention
What the sources say
- Not checked yetcites [41] Büttner-Ennever JA Anatomy of the oculomotor system Dev Ophthalmol 2007 40 1 14 17314476 source
- Not checked yetcites [42] McCrea RA Horn AKE Nucleus prepositus Prog Brain Res 2006 151 205 230 16221590 source
- Not checked yetcites [43] Gandhi NJ Katnani HA Motor functions of the superior colliculus Annu Rev Neurosci 2011 34 205 231 21456962 PMC3641825 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
In the paper
“Additionally, we have mapped OXTR and AVPR1a in the brain of the socially monogamous coppery titi monkey (Callicebus cupreus) (35).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > The value and challenges of characterising OXTR and AVPR1a distributions in the brain
What the sources say
- Not checked yetcites [35] Freeman SM Walum H Inoue K Smith AL Goodman MM Bales KL Young LJ Neuroanatomical distribution of oxytocin and vasopressin 1a receptors in the socially monogamous coppery titi monkey (Callicebus cupreus) Neuroscience 2014 273 12 23 24814726 PMC4083847 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“However, the dense OXTR binding seen in the NAcc of the common marmoset (30) makes marmosets a particularly appropriate choice for exploring the role of OT in social reward, which would complement recent discoveries in mice (25).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Evolutionary perspectives on central OXTR distributions > OXTR in primates is concentrated in brain regions involved in visual processing and attention
What the sources say
- Not checked yetcites [30] Schorscher-Petcu A Dupré A Tribollet E Distribution of vasopressin and oxytocin binding sites in the brain and upper spinal cord of the common marmoset Neurosci Lett 2009 461 217 222 19539696 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Accordingly, regions expressing OXTR in the rodent brain are most frequently found in areas of the olfactory pathway (Fig. 1a,b).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Evolutionary perspectives on central OXTR distributions > OXTR in rodents is concentrated in brain regions involved in olfactory processing
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In monogamous titi monkeys, there is remarkably dense OXTR binding in the dentate gyrus of the hippocampus (35), although the function of this population of OXTR is unknown.”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Evolutionary perspectives on central OXTR distributions > OXTR in primates is concentrated in brain regions involved in visual processing and attention
What the sources say
- Not checked yetcites [35] Freeman SM Walum H Inoue K Smith AL Goodman MM Bales KL Young LJ Neuroanatomical distribution of oxytocin and vasopressin 1a receptors in the socially monogamous coppery titi monkey (Callicebus cupreus) Neuroscience 2014 273 12 23 24814726 PMC4083847 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 4
- It may state two separate claims as one. 27
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This concept is not new; several previous studies suggested that the effects of OT and AVP are a result of the activation of the ‘opposite’ receptor (4,80,86-89).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Implications of knowing OXTR and AVPR1a distributions in NHP > Ligands for behavioural neuropharmacology of the OT system in primates
What the sources say
- Not checked yetcites [4] Takayanagi Y Yoshida M Bielsky IF Ross HE Kawamata M Onaka T Yanagisawa T Kimura T Matzuk MM Young LJ Nishimori K Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice Proc Natl Acad Sci USA 2005 102 16096 16101 16249339 PMC1276060 source
- Not checked yetcites [80] Liu N Hadj-Bouziane F Jones KB Turchi JN Averbeck BB Ungerleider LG Oxytocin modulates fMRI responses to facial expression in macaques Proc Natl Acad Sci USA 2015 112 E3123 E3130 26015576 PMC4475931 source
- Not checked yetcites [86] Ragnauth AK Goodwillie A Brewer C Muglia LJ Pfaff DW Kow L-M Vasopressin stimulates ventromedial hypothalamic neurons via oxytocin receptors in oxytocin gene knockout male and female mice Neuroendocrinology 2004 80 92 99 15528951 source
- Partly supportedcites [87] Gupta J Russell R Wayman C Hurley D Jackson V Oxytocin-induced contractions within rat and rabbit ejaculatory tissues are mediated by vasopressin V1A receptors and not oxytocin receptors Br J Pharmacol 2008 155 118 126 18552879 PMC2527840 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says oxytocin can activate the vasopressin V1A receptor and reports that both oxytocin- and AVP-induced contractions in rat and rabbit ejaculatory tissues were mediated by V1A. It does not show AVP acting through the opposite, oxytocin receptor; the claim also generalizes beyond the tissues studied. (LLM, conf=0.86)
- Supportedcites [88] Schorscher-Petcu A Sotocinal S Ciura S Dupré A Ritchie J Sorge RE Crawley JN Hu S-B Nishimori K Young LJ Tribollet E Quirion R Mogil JS Oxytocin-induced analgesia and scratching are mediated by the vasopressin-1A receptor in the mouse J Neurosci 2010 30 8274 8284 20554879 PMC2902996 source
The Introduction (page unavailable) states that both oxytocin and vasopressin can activate both receptors. The Results section on receptor antagonists (page unavailable) further shows that oxytocin-induced analgesia in mice was prevented by a vasopressin-1A receptor antagonist, supporting this paper as an example of an effect mediated by the ‘opposite’ receptor. (LLM, conf=0.88)
- Not checked yetcites [89] Song EZ McCann KE McNeill JKIV Huhman KL Albers HE Oxytocin Induces Social Communication in Male Syrian Hamsters by Activating V1a and not OT Receptors Society for Neurosceince Annual Meeting San Diego, CA 2013
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“OXTR expression across primate species has also been found in two major cholinergic regions of the brain: in all four species, in the nucleus basalis of Meynert (NBM) (Fig. 2) and, in rhesus macaques, in the pedunculopontine tegmental nucleus (PPT).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Evolutionary perspectives on central OXTR distributions > OXTR in primates is concentrated in brain regions involved in visual processing and attention
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In the primary visual path from the retina, OXTR has been detected in the superior colliculus (SC), pulvinar (Pv) and primary visual cortex (interestingly, AVPR1a binding has also been detected in many these regions) (Table 1).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Evolutionary perspectives on central OXTR distributions > OXTR in primates is concentrated in brain regions involved in visual processing and attention
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Similar experiments could also be performed in titi monkeys, which are socially monogamous but, unexpectedly, do not exhibit OXTR binding in the NAcc (Fig. 3b).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Implications of knowing OXTR and AVPR1a distributions in NHP > Site-specific injections of OT-related compounds into the brain
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the 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).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Implications of knowing OXTR and AVPR1a distributions in NHP > Site-specific injections of OT-related compounds into the brain
What the sources say
- Not checked yetcites [27] Freeman SM Inoue K Smith AL Goodman MM Young LJ The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta) Psychoneuroendocrinology 2014 45 128 141 24845184 PMC4043226 source
- Not checked yetcites [31] Young LJ Toloczko D Insel TR Localization of vasopressin (V1a) receptor binding and mRNA in the rhesus monkey brain J Neuroendocrinol 1999 11 291 297 10223283 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Instead, titi monkeys have AVPR1a expression in the NAcc (Fig. 3c) and extremely dense OXTR binding in the dentate gyrus (Fig. 3d) of the hippocampus (35).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Implications of knowing OXTR and AVPR1a distributions in NHP > Site-specific injections of OT-related compounds into the brain
What the sources say
- Not checked yetcites [35] Freeman SM Walum H Inoue K Smith AL Goodman MM Bales KL Young LJ Neuroanatomical distribution of oxytocin and vasopressin 1a receptors in the socially monogamous coppery titi monkey (Callicebus cupreus) Neuroscience 2014 273 12 23 24814726 PMC4083847 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the 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).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > The value and challenges of characterising OXTR and AVPR1a distributions in the brain
What the sources say
- Not checked yetcites [27] Freeman SM Inoue K Smith AL Goodman MM Young LJ The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta) Psychoneuroendocrinology 2014 45 128 141 24845184 PMC4043226 source
- Not checked yetcites [28] Manning M Misicka A Olma A Bankowski K Stoev S Chini B Durroux T Mouillac B Corbani M Guillon G Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics J Neuroendocrinol 2012 24 609 628 22375852 PMC3490377 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The earliest radioligand available for this purpose was a tritiated version of OT (14), although the cross-reactivity of this ligand with the closely-related AVPR1a, combined with long exposure times needed on film before results can be attained, caused it to be an unfavourable and generally inconvenient tool for autoradiographic analysis of the brain.”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > The value and challenges of characterising OXTR and AVPR1a distributions in the brain
What the sources say
- Not checked yetcites [14] Freund-Mercier MJ Stoeckel ME Palacios JM Pazos A Reichhart JM Porte A Richard P Pharmacological characteristics and anatomical distribution of [3H]oxytocin-binding sites in the Wistar rat brain studied by autoradiography Neuroscience 1987 20 599 614 3647280 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Specifically, there has been a significant gap in the understanding of the neural systems responsive to OT and AVP in primates, and the use of intranasal OT (IN-OT) in humans, in particular, has advanced rapidly despite a lack of knowledge of the mechanism or neurological targets engaged by this manipulation (11-13).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Abstract
What the sources say
- Not checked yetcites [11] Walum H Waldman ID Young LJ Statistical and methodological considerations for the interpretation of intranasal oxytocin studies Biol Psychiatry 2015 79 251 257 26210057 PMC4690817 source
- Not checked yetcites [12] Leng G Ludwig M Intranasal oxytocin: myths and delusions Biol Psychiatry 2015 79 243 250 26049207 source
- Not checked yetcites [13] Insel TR Translating oxytocin neuroscience to the clinic: a National Institute of Mental Health perspective Biol Psychiatry 2016 79 153 154 26723108 source
plain- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It has been shown that infants, toddlers and adolescents with autism spectrum disorder (ASD) all show disrupted patterns of eye movements in response to images/videos of human faces or naturalistic social scenes, including avoidance of the eye region of faces, atypical fixation targets to the nonsocial aspects of social scenes and a lack of attentional bias toward faces, as measured by faster sacc”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Clinical relevance of OXTR expression in primate visual circuits
What the sources say
- Not checked yetcites [61] Rice K Moriuchi JM Jones W Klin A Parsing heterogeneity in autism spectrum disorders: visual scanning of dynamic social scenes in school-aged children J Am Acad Child Adolesc Psychiatry 2012 51 238 248 22365460 PMC3306820 source
- Not checked yetcites [62] Chawarska K Volkmar F Klin A Limited attentional bias for faces in toddlers with autism spectrum disorders Arch Gen Psychiatry 2010 67 178 185 20124117 PMC4871149 source
- Not checked yetcites [63] Jones W Carr K Klin A Absence of preferential looking to the eyes of approaching adults predicts level of social disability in 2-year-old toddlers with autism spectrum disorder Arch Gen Psychiatry 2008 65 946 954 18678799 source
- Not checked yetcites [64] Klin A Jones W Schultz R Volkmar F Cohen D Visual fixation patterns during viewing of naturalistic social situations as predictors of social competence in individuals with autism Arch Gen Psychiatry 2002 59 809 816 12215080 source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These nuclei are major sources of cholinergic input to the rest of the brain (44-46) and are important regulators of selective attention and motivation (47-52).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Evolutionary perspectives on central OXTR distributions > OXTR in primates is concentrated in brain regions involved in visual processing and attention
What the sources say
- Not checked yetcites [44] Mesulam MM Mufson EJ Levey AI Wainer BH Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey J Comp Neurol 1983 214 170 197 6841683 source
- Not checked yetcites [45] Garcia-Rill E The pedunculopontine nucleus Prog Neurobiol 1991 36 363 389 1887068 source
- Not checked yetcites [46] Jones EG Burton H Saper CB Swanson LW Midbrain, diencephalic and cortical relationships of the basal nucleus of Meynert and associated structures in primates J Comp Neurol 1976 167 385 419 818134 source
- Not checked yetcites [47] Demeter E Sarter M Leveraging the cortical cholinergic system to enhance attention Neuropharmacology 2013 64 294 304 22796110 PMC3445745 source
- Not checked yetcites [48] Sarter M Gehring WJ Kozak R More attention must be paid: the neurobiology of attentional effort Brain Res Rev 2006 51 145 160 16530842 source
- Not checked yetcites [49] Balducci C Nurra M Pietropoli A Samanin R Carli M Reversal of visual attention dysfunction after AMPA lesions of the nucleus basalis magnocellularis (NBM) by the cholinesterase inhibitor donepezil and by a 5-HT1A receptor antagonist WAY 100635 Psychopharmacology 2003 167 28 36 12618916 source
- Not checked yetcites [50] Sarter M Givens B Bruno JP The cognitive neuroscience of sustained attention: where top-down meets bottom-up Brain Res Brain Res Rev 2001 35 146 160 11336780 source
- Not checked yetcites [51] Muir JL Page KJ Sirinathsinghji DJ Robbins TW Everitt BJ Excitotoxic lesions of basal forebrain cholinergic neurons: effects on learning, memory and attention Behav Brain Res 1993 57 123 131 7509608 source
- Not checked yetcites [52] Kobayashi Y Inoue Y Yamamoto M Isa T Aizawa H Contribution of pedunculopontine tegmental nucleus neurons to performance of visually guided saccade tasks in monkeys J Neurophysiol 2002 88 715 731 12163524 source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Furthermore, cholinergic input from the PPT strongly innervates the macaque SC (53), and neurones in the PPT have also been shown to be active in monkeys during saccade tasks (54) and to directly stimulate SC neurones and facilitate the initiation of saccadic eye movements (55).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Evolutionary perspectives on central OXTR distributions > OXTR in primates is concentrated in brain regions involved in visual processing and attention
What the sources say
- Not checked yetcites [53] Ma TP Graybiel AM Wurtz RH Location of saccade-related neurons in the macaque superior colliculus Exp Brain Res 1991 85 21 35 1715825 source
- Not checked yetcites [54] Okada K-I Kobayashi Y Characterization of oculomotor and visual activities in the primate pedunculopontine tegmental nucleus during visually guided saccade tasks Eur J Neurosci 2009 30 2211 2223 20128856 source
- Not checked yetcites [55] Kobayashi Y Saito Y Isa T Facilitation of saccade initiation by brain-stem cholinergic system Brain Dev 2001 23 Suppl 1 S24 S27 11738837 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The Pv has also been implicated in the salience of visual stimuli (40).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Evolutionary perspectives on central OXTR distributions > OXTR in primates is concentrated in brain regions involved in visual processing and attention
What the sources say
- Not checked yetcites [40] Robinson DL Petersen SE The pulvinar and visual salience Trends Neurosci 1992 15 127 132 1374970 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Activity in the right amygdala was increased in these patients in response to presentation of images of faces with direct gaze compared to averted gaze (38,39), and this activity co-varied in a condition-dependent way with activity in the SC and Pv (38).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Evolutionary perspectives on central OXTR distributions > OXTR in primates is concentrated in brain regions involved in visual processing and attention
What the sources say
- Not checked yetcites [38] Morris JS DeGelder B Weiskrantz L Dolan RJ Differential extrageniculostriate and amygdala responses to presentation of emotional faces in a cortically blind field Brain 2001 124 1241 1252 11353739 source
- Not checked yetcites [39] Burra N Hervais-Adelman A Kerzel D Tamietto M de Gelder B Pegna AJ Amygdala activation for eye contact despite complete cortical blindness J Neurosci 2013 33 10483 10489 23785160 PMC6618602 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Furthermore, NBM projects to the amygdala and is the primary source of cholinergic input to the basolateral amygdala (44,46,56,57).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Evolutionary perspectives on central OXTR distributions > OXTR in primates is concentrated in brain regions involved in visual processing and attention
What the sources say
- Not checked yetcites [44] Mesulam MM Mufson EJ Levey AI Wainer BH Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey J Comp Neurol 1983 214 170 197 6841683 source
- Not checked yetcites [46] Jones EG Burton H Saper CB Swanson LW Midbrain, diencephalic and cortical relationships of the basal nucleus of Meynert and associated structures in primates J Comp Neurol 1976 167 385 419 818134 source
- Not checked yetcites [56] Woolf NJ Butcher LL Cholinergic projections to the basolateral amygdala: a combined Evans Blue and acetylcholinesterase analysis Brain Res Bull 1982 8 751 763 6182963 source
- Not checked yetcites [57] Nagai T Kimura H Maeda T McGeer PL Peng F McGeer EG Cholinergic projections from the basal forebrain of rat to the amygdala J Neurosci 1982 2 513 520 7069469 PMC6564247 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Titi monkeys, similar to prairie voles, form lasting pair bonds and are highly territorial, which renders this species an excellent primate model for similar questions of nonapeptide function in social and spatial memory.”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Evolutionary perspectives on central OXTR distributions > OXTR in primates is concentrated in brain regions involved in visual processing and attention
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“This cholinergic input is required for memory consolidation (58,59), possibly promoting the encoding of memory during sustained attention to visual stimuli.”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Evolutionary perspectives on central OXTR distributions > OXTR in primates is concentrated in brain regions involved in visual processing and attention
What the sources say
- Not checked yetcites [58] Power AE Vazdarjanova A McGaugh JL Muscarinic cholinergic influences in memory consolidation Neurobiol Learn Mem 2003 80 178 193 14521862 source
- Not checked yetcites [59] Power AE McGaugh JL Phthalic acid amygdalopetal lesion of the nucleus basalis magnocellularis induces reversible memory deficits in rats Neurobiol Learn Mem 2002 77 372 388 11991764 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings provide new insights into the diversity and conservation of OT and AVP function in the primate brain and contrast with findings from rodent studies.”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > The value and challenges of characterising OXTR and AVPR1a distributions in the brain
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: Conserved oxytocin receptor expression regions across primates have comparable functional roles relevant to social behaviour.
In the paper
“The Merck compound L-368,899 is another small molecule OXTR antagonist that has been used in NHP studies (93), has excellent bioavailability after oral administration (94) and has been also reported to accumulate in limbic structures of the brains of rhesus macaques after peripheral injection (95).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Implications of knowing OXTR and AVPR1a distributions in NHP > Ligands for behavioural neuropharmacology of the OT system in primates
What the sources say
- Not checked yetcites [93] Smith AS Ågmo A Birnie AK French JA Manipulation of the oxytocin system alters social behavior and attraction in pair-bonding primates, Callithrix penicillata Horm Behav 2010 57 255 262 20025881 PMC2824532 source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Current studies in progress in rhesus macaques have found that OT delivered directly to the NBM changed social looking behaviour, as well as neural activity, in the basolateral amygdala (84), which is an area that lacks OXTR mRNA but receives strong cholinergic input from the NBM.”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Implications of knowing OXTR and AVPR1a distributions in NHP > Informing the design of experiments in NHP
What the sources say
- Not checked yetcites [84] Putnam P Zimmerman P Gothard K Oxytocin injected into the nucleus basalis of Meynert of monkeys enhanced basic social behaviors and modulated neural activity in the basolateral nuclei of the amygdala Gordon Research Conference. New Frontiers in Amygdala Research: From Rodent to Man Easton, MA 2015
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“First, the mixed selectivity issue within the study of OT and AVP in primates suggests that many of the effects of OT could be mediated by AVPR1a, and vice versa.”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Implications of knowing OXTR and AVPR1a distributions in NHP > Ligands for behavioural neuropharmacology of the OT system in primates
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Melanotan-II, an MC4R agonist, given peripherally, activates OT neurones and potentiates central OT release following a physiological stimulus (103).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Implications of knowing OXTR and AVPR1a distributions in NHP > Ligands for behavioural neuropharmacology of the OT system in primates
What the sources say
- Not checked yetcites [103] Modi ME Inoue K Barrett CE Kittelberger KA Smith DG Landgraf R Young LJ Melanocortin receptor agonists facilitate oxytocin-dependent partner preference formation in the prairie vole Neuropsychopharmacology 2015 40 1856 1865 25652247 PMC4839509 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The Merck compound L-368,899 is another small molecule OXTR antagonist that has been used in NHP studies (93), has excellent bioavailability after oral administration (94) and has been also reported to accumulate in limbic structures of the brains of rhesus macaques after peripheral injection (95).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Implications of knowing OXTR and AVPR1a distributions in NHP > Ligands for behavioural neuropharmacology of the OT system in primates
What the sources say
- Not checked yetcites [95] Boccia ML Goursaud A-PS Bachevalier J Anderson KD Pedersen CA Peripherally administered non-peptide oxytocin antagonist, L368,899, accumulates in limbic brain areas: a new pharmacological tool for the study of social motivation in non-human primates Horm Behav 2007 52 344 351 17583705 PMC2712625 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“New studies are now revealing receptor distributions and developing selective agents.”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Conclusions
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“IN-OT studies even in humans are often underpowered given the modest effect sizes, making the interpretation of studies with few subjects unreliable (11).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Conclusions
What the sources say
- Not checked yetcites [11] Walum H Waldman ID Young LJ Statistical and methodological considerations for the interpretation of intranasal oxytocin studies Biol Psychiatry 2015 79 251 257 26210057 PMC4690817 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Second, NHP can be used to more precisely understand OT function in the brain than is currently possible using IN-OT in humans, which is useful for understanding the mechanisms by which IN-OT influences behaviour.”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These advancements have remarkable implications not only for basic behavioural neurobiology and social neuroscience in NHP, but also for honing pharmacological therapies that may improve social cognition in psychiatric disorders, such as ASD and schizophrenia.”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Rests on an assumption: Targeting the OT system can improve social cognition in psychiatric disorders such as ASD and schizophrenia.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neurohypophyseal receptor distributions in NHP display species differences, as well as a conserved core distribution related to the importance of visual processing of social stimuli.”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Conclusions
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Although intranasal delivery of OT in NHP more accurately models current human IN-OT studies, this approach does not provide information on whether the effects are mediated by central or peripheral receptors, or whether they are mediated by OXTR or AVPR1a (12).”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Conclusions
What the sources say
- Not checked yetcites [12] Leng G Ludwig M Intranasal oxytocin: myths and delusions Biol Psychiatry 2015 79 243 250 26049207 source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Research on the role of OT and AVP in regulating social behaviour and cognition in NHP is in its infancy, far behind the level of precision found in rodent research.”
§ Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications > Conclusions
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Nonhuman primate models of social functioning can yield knowledge that translates to human oxytocin and vasopressin neurobiology.
“there is great potential to fill the gaps in our knowledge by developing better nonhuman primate models of social functioning.”
The paper relies on this without support.
Conserved oxytocin receptor expression regions across primates have comparable functional roles relevant to social behaviour.
“with perspectives on the functionality of conserved regions of expression in these distinct mammalian clades.”
The paper relies on this without support.
A tool must not interact with other behaviourally relevant neurochemical systems to isolate OT function.
“Although MC4R agonists show promise for eliciting OT-mediated behaviours, they also interact with other behaviourally relevant neurochemical systems (23) and thus are not useful tools for isolating OT function.”
The paper relies on this without support.
Targeting the OT system can improve social cognition in psychiatric disorders such as ASD and schizophrenia.
“These advancements have remarkable implications not only for basic behavioural neurobiology and social neuroscience in NHP, but also for honing pharmacological therapies that may improve social cognition in psychiatric disorders, such as ASD and schizophrenia.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Based on this connectivity of the NBM, we and others have postulated that OXT acting at OXTR in the NBM could modulate the activity of an extensive network of brain areas (which may themselves lack OXTR) and influence social behavioral processes like social visual attention, gaze direction, and social decision making38,39,64,65.”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [39]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Prairie voles and other monogamous species, including marmosets and humans express high levels of oxytocin receptors (OXTR) in the NAc while non-monogamous species, such as laboratory mice and rhesus macaques, do not 24–26.”
From Social experience alters oxytocinergic modulation in the nucleus accumbens of female prairie voles (2022) · cites this paper as [25]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Comparative studies have revealed remarkable species diversity in receptor distribution in the brain (Figure 2), likely contributing to species-specific social behaviors”
From Oxytocin, Neural Plasticity, and Social Behavior (2021) · cites this paper as Freeman & Young 2016
In the citing paper
“the two areas that have been shown to contain OXTR across all nonhuman primates studied to date39: the nucleus basalis of Meynert (NBM) in the basal forebrain and the superior colliculus (SC) of the midbrain.”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [39]
In the citing paper
“Because OXTR binding in primate brains is limited to a small number of subcortical areas and putatively absent in the cortex35,39”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [39]
In the citing paper
“Although these studies and others59–61 indicate that OXTR mRNA can be measured in some portions of the human cortex, autoradiographic studies of OXTR binding have not generated complementary evidence of functional, cell-surface OXTR in these regions of the cortex in humans35 or in nonhuman primates39.”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [39]
In the citing paper
“However, these seemingly opposing findings can be reconciled in light of our evidence for OXTR expression in the NBM of humans (current study and ref. 35) and nonhuman primates39.”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [39]
In the citing paper
“Inter- and intraspecies variation in social behavior is related to variation in the distribution of oxytocin and vasopressin receptors in the brain [10,11].”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [11]
In the citing paper
“The medial and basolateral amygdala both project to the hippocampus, which expresses oxytocin receptors and is necessary for social recognition and memory formation [5,11].”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [11]
In the citing paper
“Despite tremendous variation in social behavior across species, there is remarkable conservation in the neuromodulators regulating social behaviors.”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [11]
In the citing paper
“Oxytocin and vasopressin, for example, modulate social behaviors across vertebrate taxa, from flocking in birds to pair-bonding in voles.”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [11]
In the citing paper
“The interactions with the oxytocin system extend beyond the opioid pathway, including the dopaminergic17,18 and muscarinic acetylcholine12,19 circuits, with possible implications for social behavior and psychiatric disorders.”
From Oxytocin pathway gene networks in the human brain (2019) · cites this paper as [19]
Citations
Cites
Frequency Dependence of Signal Power and Spatial Reach of the Local Field Potential
Leski, S., Lindén, H., Tetzlaff, T., Pettersen, K. H., & Einevoll, G. T. (2013) · PubMed · doi:10.18154/rwth-conv-084442 · Cited by 3,667
Klin, A., Jones, W., Schultz, R., Volkmar, F., & Cohen, D. (2002) · Archives of General Psychiatry · doi:10.1001/archpsyc.59.9.809 · Cited by 2,120 · cited 2×
“More severe disruptions in eye movements and social visual attention in ASD patients correlate with the intensity of social dysfunction (63,64).”
BackgroundThe eyes have it: the neuroethology, function and evolution of social gaze
Emery, N. J. (2000) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(00)00025-7 · Cited by 2,037
Mesulam, M. ‐., Mufson, E. J., Levey, A. I., & Wainer, B. H. (1983) · Journal of Comparative Neurology · doi:10.1002/cne.902140206 · Cited by 1,962 · cited 2×
“These nuclei are major sources of cholinergic input to the rest of the brain (44-46) and are important Freeman and Young Page 5”
BackgroundOxytocin, vasopressin, and the neurogenetics of sociality
Donaldson, Z. R., & Young, L. J. (2008) · Science · doi:10.1126/science.1158668 · Cited by 1,645 · cited 1×
“Interestingly, OXTR binding in the NAcc, which is dense in monogamous prairie voles, is low to absent in the nonmonogamous but closely-related meadow and montane voles (19), which suggests that species-specific differences in neural distributions of OXTR can reflect the social organisation of the species (20,21).”
BackgroundSelf-citationThe neurobiology of pair bonding.
Young, L. J., & Wang, Z. (2004) · Nature Neuroscience · doi:10.1038/nn1327 · Cited by 1,523 · cited 1×
“Interestingly, OXTR binding in the NAcc, which is dense in monogamous prairie voles, is low to absent in the nonmonogamous but closely-related meadow and montane voles (19), which suggests that species-specific differences in neural distributions of OXTR can reflect the social organisation of the species (20,21).”
BackgroundThe cognitive neuroscience of sustained attention: where top-down meets bottom-up.
Sarter, M., Givens, B., & Bruno, J. P. (2001) · Brain Research Reviews · doi:10.1016/s0165-0173(01)00044-3 · Cited by 1,194
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 · cited 2×
“However, the dense OXTR binding seen in the NAcc of the common marmoset (30) makes marmosets a particularly appropriate choice for exploring the role of OT in social reward, which would complement recent discoveries in mice (25).”
BackgroundSocial amnesia in mice lacking the oxytocin gene
Ferguson, J. N., Young, L. J., Hearn, E. F., Matzuk, M. M., Insel, T. R., & Winslow, J. T. (2000) · Nature Genetics · doi:10.1038/77040 · Cited by 1,130 · cited 2×
“The OT and AVP systems are also involved in more subtle aspects of social cognition, including recognising individuals as familiar (8,9).”
BackgroundSelf-citationOxytocin 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 2×
“For example, in the studies in mice that demonstrated the requirement of OT in the MeA for social memory of a familiar conspecific, social memory was measured by the habituation of time spent in olfactory exploration of the stimulus animal after repeated presentations (8,24).”
BackgroundSelf-citationA role for central vasopressin in pair bonding in monogamous prairie voles
Winslow, J. T., Hastings, N., Carter, C. S., Harbaugh, C. R., & Insel, T. R. (1993) · Nature · doi:10.1038/365545a0 · Cited by 948 · cited 1×
“AVP also facilitates the expression of selective aggression, or mate guarding behaviour, in male prairie voles (7).”
BackgroundPromoting 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×
“Indeed, IN-OT has been shown to acutely increase gaze to the eye region of human faces in autistic populations (65,66), although the benefit of chronic or developmental OT exposure is only beginning to be explored (67,68).”
BackgroundOxytocin receptor distribution reflects social organization in monogamous and polygamous voles
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Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice
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“Mice with impaired OT release or signalling display impairments in maternal responsiveness (3,4).”
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“Furthermore, an elegant study using a multidisciplinary approach demonstrated that OXTR signalling tunes the auditory cortex to maximally respond to pup vocalisations, which facilitates maternal responsiveness (26).”
BackgroundCD38 is critical for social behaviour by regulating oxytocin secretion
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“Mice with impaired OT release or signalling display impairments in maternal responsiveness (3,4).”
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“More severe disruptions in eye movements and social visual attention in ASD patients correlate with the intensity of social dysfunction (63,64).”
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“Although intranasal delivery of OT in NHP more accurately models current human IN-OT studies, this approach does not provide information on whether the effects are mediated by central or peripheral receptors, or whether they are mediated by OXTR or AVPR1a (12).”
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“Activity in the right amygdala was increased in these patients in response to presentation of images of faces with direct gaze compared to averted gaze (38,39), and this activity co-varied in a conditiondependent way with activity in the SC and Pv (38).”
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“The OT and AVP systems are also involved in more subtle aspects of social cognition, including recognising individuals as familiar (8,9).”
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“Thus, it would be interesting to perform an experiment in marmosets analogous to the ones described above in prairie voles (18) demonstrating the prevention of pair-bond formation via site-specific blockade of OXTR in the NAcc.”
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“( B ) The olfactory information pathway in the rodent brain, including regions involved in social recognition (112,113).”
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“2), as well as deeper layers, and in the oculomotor nucleus (III) and the nucleus prepositus, which are two brainstem motor nuclei that control the muscles of the eye and participate in the horizontal gaze stabilisation system, respectively (41-43).”
BackgroundThe pulvinar and visual salience
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BackgroundThe biology of mammalian parenting and its effect on offspring social development
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“Work in rats has demonstrated that central OT signalling is crucial for the onset of maternal nurturing behaviour (1,2).”
BackgroundSelf-citationOxytocin and Vasopressin Agonists and Antagonists as Research Tools and Potential Therapeutics
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“Simply comparing the binding characteristics of the most common ligands for the human and rat OT and AVP receptors reveals considerable variation in pharmacological properties across species (28).”
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“These nuclei are major sources of cholinergic input to the rest of the brain (44-46) and are important Freeman and Young Page 5”
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“To our knowledge, rodent species with known OXTR and AVPR1a distributions include laboratory mice and rats, hamsters, guinea pigs, the socially monogamous California mouse and the promiscuous deer mouse, a social and a solitary species of tuco-tuco, two species of Central American singing mice, the eusocial naked mole…”
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“Work in rats has demonstrated that central OT signalling is crucial for the onset of maternal nurturing behaviour (1,2).”
BackgroundSelf-citationStatistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies
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“IN-OT studies even in humans are often underpowered given the modest effect sizes, making the interpretation of studies with few subjects unreliable (11).”
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“More severe disruptions in eye movements and social visual attention in ASD patients correlate with the intensity of social dysfunction (63,64).”
BackgroundInfluentialThe oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis
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“human OXTR gene are associated with an ASD diagnosis (71).”
BackgroundAmygdala Volume and Nonverbal Social Impairment in Adolescent and Adult Males With Autism
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“There are now several highly selective, low molecular weight, nonpeptide ligands that purportedly cross the blood-brain barrier, such as the selective human AVPR1a antagonist, SR49059 (90), and the selective human OXTR antagonist, ALS-II-69 (91,92).”
BackgroundMuscarinic cholinergic influences in memory consolidation
Power, A. (2003) · Neurobiology of Learning and Memory · doi:10.1016/s1074-7427(03)00086-8 · Cited by 261
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“In rhesus macaques, three studies have found that treatment with IN-OT impacts social visual attention and looking behaviours in a variety of tasks (77-79).”
BackgroundNasal oxytocin for social deficits in childhood autism: A randomized controlled trial
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“More severe disruptions in eye movements and social visual attention in ASD patients correlate with the intensity of social dysfunction (63,64).”
BackgroundInfluential125I-labelled d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH29]OVT: a selective oxytocin receptor ligand
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“It has been shown that infants, toddlers and adolescents with autism spectrum disorder (ASD) all show disrupted patterns of eye movements in response to images/videos of human faces or naturalistic social scenes, including avoidance of the eye region of faces, atypical fixation targets to the nonsocial aspects of soci…”
BackgroundAuyeung, B., Lombardo, M. V., Heinrichs, M., Chakrabarti, B., Sule, A., Deakin, J. B., Bethlehem, R. A. I., Dickens, L., Mooney, N., Sipple, J. A. N., et al. (2015) · Translational Psychiatry · doi:10.1038/tp.2014.146 · Cited by 234 · cited 1×
“Indeed, IN-OT has been shown to acutely increase gaze to the eye region of human faces in autistic populations (65,66), although the benefit of chronic or developmental OT exposure is only beginning to be explored (67,68).”
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“Furthermore, NBM projects to the amygdala and is the primary source of cholinergic input to the basolateral amygdala (44,46,56,57).”
BackgroundSmith, A. S., Ågmo, A., Birnie, A. K., & French, J. A. (2010) · Hormones and Behavior · doi:10.1016/j.yhbeh.2009.12.004 · Cited by 228 · cited 2×
“The Merck compound L-368,899 is another small molecule OXTR antagonist that has been used in NHP studies (93), has excellent bioavailability after oral administration (94) and has been also reported to accumulate in limbic structures of the brains of rhesus macaques after peripheral injection (95).”
BackgroundGuastella, A. J., & Hickie, I. B. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.06.028 · Cited by 223 · cited 9×
“More severe disruptions in eye movements and social visual attention in ASD patients correlate with the intensity of social dysfunction (63,64).”
BackgroundInfluentialClinical and neural effects of six-week administration of oxytocin on core symptoms of autism
Watanabe, T., Kuroda, M., Kuwabara, H., Aoki, Y., Iwashiro, N., Tatsunobu, N., Takao, H., Nippashi, Y., Kawakubo, Y., Kunimatsu, A., et al. (2015) · Brain · doi:10.1093/brain/awv249 · Cited by 222 · cited 1×
“Indeed, IN-OT has been shown to acutely increase gaze to the eye region of human faces in autistic populations (65,66), although the benefit of chronic or developmental OT exposure is only beginning to be explored (67,68).”
BackgroundYoung, L. J., & Barrett, C. E. (2015) · Science · doi:10.1126/science.aaa8120 · Cited by 200 · cited 2×
“Nevertheless, because they can be given peripherally and evoke central OT release, they could have important translational applications and are easily tested in NHP (101).”
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“regulators of selective attention and motivation (47-52).”
Maternal aggression in rodents: brain oxytocin and vasopressin mediate pup defence
Bosch, O. J. (2013) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2013.0085 · Cited by 194 · cited 1×
“Central OT and AVP signalling also modulate the expression of maternal aggression in defence of pups (5).”
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“The earliest radioligand available for this purpose was a tritiated version of OT (14), although the cross-reactivity of this ligand with the closely-related AVPR1a, combined with long exposure times needed on film before results can be attained, caused it to be an unfavourable and generally…”
BackgroundLimited Attentional Bias for Faces in Toddlers With Autism Spectrum Disorders
Katarzyna, C., Fred, V., & Ami, K. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.194 · Cited by 191 · cited 1×
“It has been shown that infants, toddlers and adolescents with autism spectrum disorder (ASD) all show disrupted patterns of eye movements in response to images/videos of human faces or naturalistic social scenes, including avoidance of the eye region of faces, atypical fixation targets to the nonsocial aspects of soci…”
BackgroundKing, 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 · cited 1×
“Furthermore, individual differences in the density of OXTR in the NAcc in prairie voles have now been shown to be mediated by a single nucleotide polymorphism (SNP) in a regulatory region of the OXTR gene (22), and individuals with high NAcc OXTR show enhanced social attachment (22) and resilience to early life stress…”
BackgroundSelf-citationSabatier, N., Caquineau, C., Dayanithi, G., Bull, P., Douglas, A. J., Guan, X. M. M., Jiang, M., Van der Ploeg, L., & Leng, G. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-32-10351.2003 · Cited by 190
Oxytocin-Induced Analgesia and Scratching Are Mediated by the Vasopressin-1A Receptor in the Mouse
Schorscher-Petcu, A., Sotocinal, S., Ciura, S., Dupre, A., Ritchie, J., Sorge, R. E., Crawley, J. N., Hu, S.-B., Nishimori, K., Young, L. J., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1594-10.2010 · Cited by 189 · cited 1×
“This concept is not new; several previous studies suggested that the effects of OT and AVP are a result of the activation of the ‘opposite’ receptor (4,80,86-89).”
BackgroundSelf-citationFreeman, 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 6×
“ALS-II-69 was evaluated in previous studies and shown to effectively block OXTR radioligand binding to primate brain tissue (27).”
BackgroundMethodInfluentialNeurobiological 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-citationLim, M. M., Murphy, A. Z., & Young, L. J. (2004) · Journal of Comparative Neurology · doi:10.1002/cne.10973 · Cited by 163 · cited 1×
“3 A ) similar to that of the prairie vole (30,85).”
BackgroundSelf-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 · cited 2×
“Recent work using site-specific infusions of OT into the macaque brain has targeted the amygdala (81,83).”
BackgroundNeurons in the Monkey Amygdala Detect Eye Contact during Naturalistic Social Interactions
Mosher, C. P., Zimmerman, P. E., & Gothard, K. M. (2014) · Current Biology · doi:10.1016/j.cub.2014.08.063 · Cited by 154 · cited 2×
“Recent studies in NHP have begun using combinations of these approaches, such as eye tracking, social viewing tasks and sitespecific neural recordings, to better understand nonhuman primate social cognition (82) and the function of OT in the NHP brain (83).”
BackgroundMethodFreeman, 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 · cited 2×
“Additionally, we have mapped OXTR and AVPR1a in the brain of the socially monogamous coppery titi monkey (Callicebus cupreus) (35).”
BackgroundSelf-citationVariant in oxytocin receptor gene is associated with amygdala volume
Furman, D. J., Chen, M. C., & Gotlib, I. H. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.12.004 · Cited by 151 · cited 1×
“One SNP (rs2254298) has also been linked to smaller amygdala volume (72), which is a neural phenotype that has also been found in ASD populations and predicts ASD symptom severity (73).”
BackgroundBeery, A. K., Lacey, E. A., & Francis, D. D. (2008) · Journal of Comparative Neurology · doi:10.1002/cne.21638 · Cited by 144 · cited 1×
“To our knowledge, rodent species with known OXTR and AVPR1a distributions include laboratory mice and rats, hamsters, guinea pigs, the socially monogamous California mouse and the promiscuous deer mouse, a social and a solitary species of tuco-tuco, two species of Central American singing mice, the eusocial naked mole…”
BackgroundCholinergic projections from the basal forebrain of rat to the amygdala
Nagai, T., Kimura, H., Maeda, T., McGeer, P., Peng, F., & McGeer, E. (1982) · The Journal of Neuroscience · doi:10.1523/jneurosci.02-04-00513.1982 · Cited by 140 · cited 1×
“Furthermore, NBM projects to the amygdala and is the primary source of cholinergic input to the basolateral amygdala (44,46,56,57).”
BackgroundLocalization of Vasopressin (V1a) Receptor Binding and mRNA in the Rhesus Monkey Brain
Young, Toloczko, & Insel (1999) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.1999.00332.x · Cited by 139 · cited 2×
“Nevertheless, before these pharmacological limitations were fully understood, these radioligands (as well as the older tritiated versions of the endogenous neuropeptides themselves) were used for receptor autoradiography in three primate species: in the common marmoset for OXTR and AVPR1a (29,30), in the rhesus macaqu…”
BackgroundBoccia, M. L., Goursaud, A.-P. S., Bachevalier, J., Anderson, K. D., & Pedersen, C. A. (2007) · Hormones and Behavior · doi:10.1016/j.yhbeh.2007.05.009 · Cited by 136 · cited 1×
“The Merck compound L-368,899 is another small molecule OXTR antagonist that has been used in NHP studies (93), has excellent bioavailability after oral administration (94) and has been also reported to accumulate in limbic structures of the brains of rhesus macaques after peripheral injection (95).”
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“To our knowledge, rodent species with known OXTR and AVPR1a distributions include laboratory mice and rats, hamsters, guinea pigs, the socially monogamous California mouse and the promiscuous deer mouse, a social and a solitary species of tuco-tuco, two species of Central American singing mice, the eusocial naked mole…”
BackgroundInfluentialOxytocin 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
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 · cited 1×
“In rhesus macaques, three studies have found that treatment with IN-OT impacts social visual attention and looking behaviours in a variety of tasks (77-79).”
BackgroundSelf-citationSocial recognition memory requires two stages of protein synthesis in micePreprint
Richter, K., Wolf, G. L., & Engelmann, M. (2005) · Learning & Memory · doi:10.1101/lm.97505 · Cited by 121 · cited 1×
“( B ) The olfactory information pathway in the rodent brain, including regions involved in social recognition (112,113).”
BackgroundThe nose knows who's who: chemosensory individuality and mate recognition in mice
Brennan, P. A. (2004) · Hormones and Behavior · doi:10.1016/j.yhbeh.2004.01.010 · Cited by 120 · cited 1×
“Identification of individuals as either kin, a familiar conspecific or an unrelated potential mate of the opposite sex is based on olfactory processing of major urinary proteins (36).”
BackgroundAmygdala Activation for Eye Contact Despite Complete Cortical Blindness
Burra, N., Hervais-Adelman, A., Kerzel, D., Tamietto, M., de Gelder, B., & Pegna, A. J. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3994-12.2013 · Cited by 118 · cited 2×
“Activity in the right amygdala was increased in these patients in response to presentation of images of faces with direct gaze compared to averted gaze (38,39), and this activity co-varied in a conditiondependent way with activity in the SC and Pv (38).”
BackgroundBarrett, C. E., Arambula, S. E., & Young, L. J. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.73 · Cited by 115 · cited 3×
“Peripheral MT-II administration also facilitates OT-dependent social bonding in prairie voles and eliminates the social behaviour deficits associated with neonatal social isolation in prairie voles (23,103,104).”
BackgroundSelf-citationGonadal steroids have paradoxical effects on brain oxytocin receptors
Insel, T. R., Young, L., Witt, D. M., & Crews, D. (1993) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.1993.tb00531.x · Cited by 113 · cited 1×
“( A ) OXTR expression in select areas of the rodent brain (17,111).”
BackgroundSelf-citationSchorscher-Petcu, A., Dupré, A., & Tribollet, E. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.06.016 · Cited by 111 · cited 15×
“To our knowledge, rodent species with known OXTR and AVPR1a distributions include laboratory mice and rats, hamsters, guinea pigs, the socially monogamous California mouse and the promiscuous deer mouse, a social and a solitary species of tuco-tuco, two species of Central American singing mice, the eusocial naked mole…”
BackgroundResultInfluentialA 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 · cited 1×
“Clinical trials are in progress that aim to explore the therapeutic potential of OT in ASD (67,69), and considerable work is being carried out to examine its potential use to treat schizophrenia as well (70).”
BackgroundKobayashi, Y., Inoue, Y., Yamamoto, M., Isa, T., & Aizawa, H. (2002) · Journal of Neurophysiology · doi:10.1152/jn.2002.88.2.715 · Cited by 104 · cited 1×
“regulators of selective attention and motivation (47-52).”
McCrea, R. A., & Horn, A. K. E. (2006) · Progress in Brain Research · doi:10.1016/s0079-6123(05)51007-0 · Cited by 92 · cited 1×
“2), as well as deeper layers, and in the oculomotor nucleus (III) and the nucleus prepositus, which are two brainstem motor nuclei that control the muscles of the eye and participate in the horizontal gaze stabilisation system, respectively (41-43).”
BackgroundA novel form of oxytocin in New World monkeys
Lee, A. G., Cool, D. R., Grunwald, W. C., Neal, D. E., Buckmaster, C. L., Cheng, M. Y., Hyde, S. A., Lyons, D. M., & Parker, K. J. (2011) · Biology Letters · doi:10.1098/rsbl.2011.0107 · Cited by 91 · cited 1×
“Species differences in receptor binding characteristics vary widely, especially in light of recent discoveries in New World monkeys, which show genetic variations in both the OT and AVP peptide and receptor genes across species (105-110).”
BackgroundModi, 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 · cited 2×
“Peripheral MT-II administration also facilitates OT-dependent social bonding in prairie voles and eliminates the social behaviour deficits associated with neonatal social isolation in prairie voles (23,103,104).”
BackgroundSelf-citationEditorial 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 · cited 1×
“Without these and other foundational studies in rodents, it is unlikely that the growth rate in the number of studies examining the OT system in humans and nonhuman primates (NHP) would be as high as it is currently (10).”
BackgroundSelf-citationLeveraging the cortical cholinergic system to enhance attention
Demeter, E., & Sarter, M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.06.060 · Cited by 75 · cited 2×
“Manipulations of the muscarinic cholinergic receptor or nicotinic cholinergic receptor have been suggested as a way of enhancing attention (47).”
BackgroundWang, Z., Toloczko, D., Young, L. J., Moody, K., Newman, J. D., & Insel, T. R. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00636-7 · Cited by 75 · cited 13×
“To our knowledge, rodent species with known OXTR and AVPR1a distributions include laboratory mice and rats, hamsters, guinea pigs, the socially monogamous California mouse and the promiscuous deer mouse, a social and a solitary species of tuco-tuco, two species of Central American singing mice, the eusocial naked mole…”
BackgroundInfluentialSelf-citationCavanaugh, J., Mustoe, A. C., Taylor, J. H., & French, J. A. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.06.020 · Cited by 72 · cited 1×
“This compound is already being used in behavioural pharmacological studies in marmosets, including investigations of pair bonding and adult sociosexual behaviour (93,96,97), stress reactivity (98), and responsiveness to infant cues (99).”
BackgroundLocation of saccade-related neurons in the macaque superior colliculus
Ma, T. P., Graybiel, A. M., & Wurtz, R. H. (1991) · Experimental Brain Research · doi:10.1007/bf00229983 · Cited by 71 · cited 1×
“Furthermore, cholinergic input from the PPT strongly innervates the macaque SC (53), and neurones in the PPT have also been shown to be active in monkeys during saccade tasks (54) and to directly stimulate SC neurones and facilitate the initiation of saccadic eye movements (55).”
BackgroundTollenaar, M. S., Chatzimanoli, M., van der Wee, N. J. A., & Putman, P. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.02.018 · Cited by 68 · cited 1×
“Although the central OXTR distribution in NHP may or may not be predictive of that of humans, given the remarkable species differences in receptor distribution, evidence is building from behavioural studies in both humans (76) and NHP that IN-OT is capable of altering social visual attention.”
BackgroundOxytocin and vasopressin enhance responsiveness to infant stimuli in adult marmosets
Taylor, J. H., & French, J. A. (2015) · Hormones and Behavior · doi:10.1016/j.yhbeh.2015.10.002 · Cited by 68 · cited 1×
“This compound is already being used in behavioural pharmacological studies in marmosets, including investigations of pair bonding and adult sociosexual behaviour (93,96,97), stress reactivity (98), and responsiveness to infant cues (99).”
BackgroundGupta, J., Russell, R. J., Wayman, C. P., Hurley, D., & Jackson, V. M. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.226 · Cited by 66 · cited 1×
“This concept is not new; several previous studies suggested that the effects of OT and AVP are a result of the activation of the ‘opposite’ receptor (4,80,86-89).”
BackgroundOxytocin 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 · cited 2×
“It has also recently been shown that treatment with IN-OT in macaques can alter neural responses to emotional faces (80).”
BackgroundOxytocin modulates behavioral and physiological responses to a stressor in marmoset monkeys
Cavanaugh, J., Carp, S. B., Rock, C. M., & French, J. A. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.12.027 · Cited by 64 · cited 1×
“This compound is already being used in behavioural pharmacological studies in marmosets, including investigations of pair bonding and adult sociosexual behaviour (93,96,97), stress reactivity (98), and responsiveness to infant cues (99).”
BackgroundVargas-Pinilla, P., Paixão-Côrtes, V. R., Paré, P., Tovo-Rodrigues, L., Vieira, C. M. D. A. G., Xavier, A., Comas, D., Pissinatti, A., Sinigaglia, M., Rigo, M. M., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1419399112 · Cited by 59 · cited 1×
“Species differences in receptor binding characteristics vary widely, especially in light of recent discoveries in New World monkeys, which show genetic variations in both the OT and AVP peptide and receptor genes across species (105-110).”
BackgroundAnatomy of the Oculomotor System
Büttner-Ennever, J. A. (2007) · Developments in Ophthalmology · doi:10.1159/000100345 · Cited by 57 · cited 1×
“2), as well as deeper layers, and in the oculomotor nucleus (III) and the nucleus prepositus, which are two brainstem motor nuclei that control the muscles of the eye and participate in the horizontal gaze stabilisation system, respectively (41-43).”
BackgroundPower, A. E., & McGaugh, J. L. (2002) · Neurobiology of Learning and Memory · doi:10.1006/nlme.2001.4030 · Cited by 57 · cited 1×
“This cholinergic input is required for memory consolidation (58,59), possibly promoting the encoding of memory during sustained attention to visual stimuli.”
BackgroundTranslating 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 · cited 1×
“that can selectively and reliably reveal the distributions of OXTR and AVPR1a in primate tissue (27). 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 biomedica…”
ResultWallis, M. (2012) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2012.07.030 · Cited by 48 · cited 1×
“Species differences in receptor binding characteristics vary widely, especially in light of recent discoveries in New World monkeys, which show genetic variations in both the OT and AVP peptide and receptor genes across species (105-110).”
BackgroundGenetic Diversity in Oxytocin Ligands and Receptors in New World Monkeys
Ren, D., Lu, G., Moriyama, H., Mustoe, A. C., Harrison, E. B., & French, J. A. (2015) · PLOS ONE · doi:10.1371/journal.pone.0125775 · Cited by 47 · cited 1×
“Species differences in receptor binding characteristics vary widely, especially in light of recent discoveries in New World monkeys, which show genetic variations in both the OT and AVP peptide and receptor genes across species (105-110).”
BackgroundProunis, G. S., Foley, L., Rehman, A., & Ophir, A. G. (2015) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2015.2236 · Cited by 44 · cited 1×
“The distribution of OXTR (and AVPR1a) is now being investigated in monogamous prairie voles with the aim of understanding how patterns of receptor expression may contribute to sociospatial memory (60).”
BackgroundBalducci, C., Nurra, M., Pietropoli, A., Samanin, R., & Carli, M. (2003) · Psychopharmacology · doi:10.1007/s00213-002-1385-7 · Cited by 42 · cited 1×
“regulators of selective attention and motivation (47-52).”
Ragnauth, A. K., Goodwillie, A., Brewer, C., Muglia, L. J., Pfaff, D. W., & Kow, L.-M. (2004) · Neuroendocrinology · doi:10.1159/000081844 · Cited by 41 · cited 1×
“This concept is not new; several previous studies suggested that the effects of OT and AVP are a result of the activation of the ‘opposite’ receptor (4,80,86-89).”
BackgroundPharmacokinetics and disposition of the oxytocin receptor antagonist L-368,899 in rats and dogs.
Thompson, K. L., Vincent, S. H., Miller, R. R., Colletti, A. E., Alvaro, R. F., Wallace, M. A., Feeney, W. P., & Chiu, S. H. (1997) · PubMed · Cited by 41
Smith, A. L., Freeman, S. M., Voll, R. J., Young, L. J., & Goodman, M. M. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2012.10.116 · Cited by 38 · cited 1×
“However, after radiolabelling L-368,899 and performing in vivo PET imaging in macaques, we found that there is minimal uptake in the brain, and the compound appears to accumulate in the ventricles and not in neural tissue (100).”
BackgroundSelf-citationMarmosets 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 · cited 1×
“This compound is already being used in behavioural pharmacological studies in marmosets, including investigations of pair bonding and adult sociosexual behaviour (93,96,97), stress reactivity (98), and responsiveness to infant cues (99).”
BackgroundSmith, A. L., Freeman, S. M., Stehouwer, J. S., Inoue, K., Voll, R. J., Young, L. J., & Goodman, M. M. (2012) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2012.02.019 · Cited by 35 · cited 3×
“We have also developed other novel, small-molecule, highly selective OXTR antagonists as tools for behavioural pharmacology in NHP, as well as for potential tracers for in vivo positron emission tomography (PET) neuroimaging (91,92).”
BackgroundSelf-citationBarrett, C. E., Modi, M. E., Zhang, B. C., Walum, H., Inoue, K., & Young, L. J. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.05.041 · Cited by 34
Self-citationAre there oxytocin receptors in the primate brain?
TOLOCZKO, D. M., YOUNG, L., & INSEL, T. R. (1997) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1997.tb51953.x · Cited by 33 · cited 1×
“The mapping of OXTR in the macaque brain was previously attempted in the 1990s but abandoned because of the apparent nonselectivity of 125I-OVTA (34).”
BackgroundSelf-citationElands, J., Barberis, C., Jard, S., Lammek, B., Manning, M., Sawyer, W. H., & de Kloet, E. R. (1988) · FEBS Letters · doi:10.1016/0014-5793(88)81135-9 · Cited by 28 · cited 1×
“Later, highly selective radiolabelled peptide analogues for OXTR and AVPR1a binding were developed for use in rodent brain tissue (15,16).”
BackgroundInvestigation of an F-18 oxytocin receptor selective ligand via PET imaging
Smith, A. L., Freeman, S. M., Voll, R. J., Young, L. J., & Goodman, M. M. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.07.045 · Cited by 28 · cited 3×
“We have also developed other novel, small-molecule, highly selective OXTR antagonists as tools for behavioural pharmacology in NHP, as well as for potential tracers for in vivo positron emission tomography (PET) neuroimaging (91,92).”
BackgroundSelf-citationOkada, K., & Kobayashi, Y. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.07009.x · Cited by 28
Ren, D., Chin, K. R., & French, J. A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111638 · Cited by 28 · cited 1×
“Species differences in receptor binding characteristics vary widely, especially in light of recent discoveries in New World monkeys, which show genetic variations in both the OT and AVP peptide and receptor genes across species (105-110).”
BackgroundFacilitation of saccade initiation by brainstem cholinergic system
Kobayashi, Y., Saito, Y., & Isa, T. (2001) · Brain and Development · doi:10.1016/s0387-7604(01)00330-8 · Cited by 26 · cited 1×
“Furthermore, cholinergic input from the PPT strongly innervates the macaque SC (53), and neurones in the PPT have also been shown to be active in monkeys during saccade tasks (54) and to directly stimulate SC neurones and facilitate the initiation of saccadic eye movements (55).”
BackgroundIdentification of prepositus neurons projecting to the oculomotor nucleus in the alert cat
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“Species differences in receptor binding characteristics vary widely, especially in light of recent discoveries in New World monkeys, which show genetic variations in both the OT and AVP peptide and receptor genes across species (105-110).”
BackgroundNucleus Prepositus Neurons Projecting to the Oculomotor and Trochlear Nuclei in Rabbits
Labandeira-García, J. L., Guerra-Seijas, M. J., & Labandeira-García, J. (2008) · Brain Behavior and Evolution · doi:10.1159/000115852 · Cited by 5
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Oxytocin, Neural Plasticity, and Social Behavior
Froemke, R. C., & Young, L. J. (2021) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-102320-102847 · Cited by 480
“Comparative studies have revealed remarkable species diversity in receptor distribution in the brain (Figure 2), likely contributing to species-specific social behaviors (Freeman & Young 2016, Johnson & Young 2017).”
BackgroundSelf-citationIs oxytocin “nature’s medicine”
Carter, C. S., Kenkel, W. M., MacLean, E. L., Wilson, S. R., Perkeybile, A. M., Yee, J. R., Ferris, C. F., Nazarloo, H. P., Porges, S. W., Davis, J. M., et al. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019398 · Cited by 394
“This, in turn, creates another source of complexity, since peptide receptors in the nervous system influence the entire body but also often differ in abundance and localization among individuals and species (Witt et al., 1991; Freeman and Young, 2016; Freeman et al., 2018).”
BackgroundInfluentialThe neural mechanisms and circuitry of the pair bond
Walum, H., & Young, L. J. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0072-6 · Cited by 353
Self-citationOxytocin pathway gene networks in the human brain
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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
Metadata
- Authors
- Freeman, S. M., & Young, L. J.
- Affiliations
- University of California, Davis (US)
- Emory University (US)
- Corresponding author
- Freeman, Sara M.
- Venue
- Journal of Neuroendocrinology
- Publisher
- Wiley
- Published
- 2016-04
- Volume
- 28
- Issue
- 4
- ISSN
- 0953-8194 (ISSN-L)
- 1365-2826
- PMC
- PMC4886472
- OpenAlex
- W2288695197
- Cited by
- 196
- References
- 114
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 15 · 2023: 13 · 2022: 18 · 2021: 17 · 2020: 32 · 2019: 12 · 2018: 30 · 2017: 22 · 2016: 16
- FWCI
- 4.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (MH090776, 1P50MH100023)
- 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, vasopressin, oxytocin receptor, vasopressin receptor, non-human primates, rodents, social behavior, social cognition, translational research, receptor distribution, intranasal oxytocin, behavioral pharmacology, receptor autoradiography, optogenetics, comparative neurobiology
- MeSH terms
- Animals, Species Specificity, Receptors, Vasopressin, Receptors, Oxytocin, Translational Research, Biomedical
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