Localization of high-affinity binding sites for oxytocin and vasopressin in the human brain. An autoradiographic study
Abstract
Sites which bind oxytocin and vasopressin with high affinity were detected in the brain and upper spinal cord of 12 human subjects, using in vitro light microscopic autoradiography. Tissue sections were incubated with tritiated vasopressin, tritiated oxytocin or an iodinated oxytocin antagonist. The ligand specificity of binding was assessed with unlabelled vasopressin or oxytocin in excess, as well as in competition experiments using synthetic structural analogues. The distribution of vasopressin binding sites differed markedly from that of oxytocin binding sites in the forebrain, while there was overlap in the brainstem. Vasopressin binding sites were detected in the dorsal part of the lateral septal nucleus, in midline nuclei and adjacent intralaminar nuclei of the thalamus, in the hilus of the dentate gyrus, the dorsolateral part of the basal amygdaloid nucleus and the brainstem. The distribution of oxytocin binding sites in the brainstem has been recently reported (Loup et al., 1989). Oxytocin binding sites were also observed in the basal nucleus of Meynert, the nucleus of the vertical limb of the diagonal band of Broca, the ventral part of the lateral septal nucleus, the preoptic/anterior hypothalamic area, the posterior hypothalamic area, and variably in the globus pallidus and ventral pallidum. The presence of oxytocin and vasopressin binding sites in limbic and autonomic areas suggests a neurotransmitter or neuromodulator role for these peptides in the human central nervous system. They may also affect cholinergic transmission in the basal forebrain and consequently play a role in Alzheimer's disease.
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The localization of OT receptors in nonhuman primates is consistent with the putative localization of OT receptors in human brain.
“consistent with the putative localization of OT receptors in human brain (44)”
From Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies (2016) · cites this paper as [44]
The brain-level attachment system is maintained in large part by the neuropeptides oxytocin and vasopressin.
“Our particular focus will be on the brain-level attachment system [30], maintained (in large part) by the neuropeptides oxytocin and vasopressin [31, 32].”
From Could intranasal oxytocin be used to enhance relationships? Research imperatives, clinical policy, and ethical considerations (2013) · cites this paper as [30]
OXTR binding in primate brains is limited to a small number of subcortical areas and putatively absent in the cortex.
“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 [35]
The neuroanatomical map of OXTR binding in the human brain has not been reliably characterized, except for two outdated studies whose results have recently been called into question due to the radioligand's high degree of cross-reactivity to AVPR1a.
“The neuroanatomical map of OXTR binding in the human brain has not been reliably characterized, except for two outdated studies35,36 whose results have recently been called into question34 due to the radioligand’s high degree of cross-reactivity to the structurally similar vasopressin 1a receptor (AVPR1a).”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [35]
All five areas contained putative OXTR binding, which agrees with the older study and supports the idea that these tools are more selective in the human brain compared to nonhuman primate brain.
“We found that all five areas contained putative OXTR binding, which agrees with what was reported in the older study (mentioned above35) and supports the idea that these tools are more selective in the human brain compared to that in a nonhuman primate brain.”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [35]
The seemingly opposing findings can be reconciled in light of evidence for OXTR expression in the NBM of humans and nonhuman primates.
“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 [35]
Although 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 humans or in nonhuman primates.
“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 [35]
Before the pharmacological limitations were understood, these radioligands were used for receptor autoradiography in the common marmoset, rhesus macaque, and human.
“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 macaque for AVPR1a (31), and in human for OXTR and AVPR1a (32,33).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [32]
The sex-specific effects of the VP system appear independent of whether sex differences in VP and/or V1aR binding are present.
“Interestingly, these sex-specific effects seem to be independent of whether sex differences are found in VP and/or V1aR binding (rats; Figs. 1 and 2) or whether no sex differences are found in VP and/or V1aR binding (prairie voles: Insel et al., 1991; Smeltzer et al., 2006; humans: Loup et al., 1991).”
From Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior (2016) · cites this paper as Loup et al., 1991
The notion that OT and VP may act at distinct brain regions to modulate social behaviors in a similar direction is supported by the distinct and non-overlapping distribution of V1aR and OTR in the brain of humans and voles.
“The notion that OT and VP may be acting at distinct brain regions to modulate social behaviors in a similar direction is further supported by the distinct and non-overlapping distribution of V1aR and OTR in the brain of humans (Loup et al., 1991) and voles (Lim et al., 2004a).”
From Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior (2016) · cites this paper as Loup et al., 1991
Both OT and AVP are released in the brain and bind to receptors there to affect social behaviors.
“In addition, both peptides are released in the brain and bind to receptors there to affect social behaviors (Buijs et al 1983; Alonso et al 1986; Loup et al 1991).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Loup et al 1991
OXTR mRNA localization in the rodent brain is well-described, but its anatomical distribution across the human brain is poorly understood because investigations have historically sampled very few brain regions.
“While OXTR mRNA localization in the rodent brain is well-described11, its anatomical distribution across the human brain is poorly understood, as investigations have historically tended to sample very few brain regions12.”
From Oxytocin pathway gene networks in the human brain (2019) · cites this paper as [12]
Interactions with the oxytocin system extend beyond the opioid pathway, including the dopaminergic and muscarinic acetylcholine circuits, with possible implications for social behavior and psychiatric disorders.
“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 [12]
Brain regions with high oxytocin pathway gene expression in humans have been identified, but inference of specific cognitive states from the activity of single brain regions is elusive.
“While brain regions with high oxytocin pathway gene expression in humans have been identified12,13, inference of specific cognitive states from the activity of single brain regions is elusive.”
From Oxytocin pathway gene networks in the human brain (2019) · cites this paper as [12]
Our findings corroborate emerging evidence for interactions between the oxytocin, acetylcholine, and dopaminergic signaling systems.
“Altogether, our findings corroborate emerging evidence for interactions between the oxytocin, acetylcholine12, and dopaminergic signaling systems17.”
From Oxytocin pathway gene networks in the human brain (2019) · cites this paper as [12]
Data from the GTEx dataset demonstrated little evidence of sex differences in central oxytocin pathway gene expression.
“data from the GTEx dataset demonstrated little evidence of sex differences in central oxytocin pathway gene expression, consistent with preliminary human research12.”
From Oxytocin pathway gene networks in the human brain (2019) · cites this paper as [12]
In Homo, V1aR was less widely distributed across the social-decision making network relative to Callithrix, Callicebus, and Macaca, although fewer brain regions were sampled.
“In Homo, V1aR was less widely distributed across the social-decision making network (Loup et al., 1991) relative to Callithrix, Callicebus, and Macaca, although fewer brain regions were sampled.”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Loup et al., 1991
Macaca showed no V1aR binding in the SC, and Homo showed no V1aR binding in either the SC or NBM.
“Macaca showed no V1aR binding in the SC, and Homo showed no V1aR binding in either the SC or NBM (Freeman et al., 2014a; Loup et al., 1991).”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Loup et al., 1991
Male and female Macaca and Homo display similar density and distribution of V1aR.
“The limited information on sex differences in V1aR shows that male and female Macaca (Young et al., 1999) and Homo (Loup et al., 1991) display similar density and distribution of V1aR.”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Loup et al., 1991
Studies in human and non-human primates have found notable differences in OT receptor distributions compared to rodents.
“Nevertheless, studies in human and non-human primates have also found some notable differences in OT receptor distributions compared to rodents (Boccia et al., 2013; Caffé et al., 1989; Jenkins et al., 1984; Loup et al., 1991).”
From Oxytocin and social cognition in rhesus macaques: Implications for understanding and treating human psychopathology (2014) · cites this paper as Loup et al., 1991
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“Likewise, there were no sex differences in V1R binding in several brain regions analyzed in humans (Loup et al., 1991), but this also remains inconclusive because 3H VP was used and the number of women was very low (n=4).. V1aR binding was also found throughout the brain of male and female…”
BackgroundResultInfluentialNeuromodulation by Oxytocin and Vasopressin
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“Several of the regions noted above (e.g. the SN, GP and thalamus) have a high density of oxytocin (OT) and vasopressin (AVP) receptors (Jenkins et al., 1984; Loup et al., 1991).”
BackgroundAutism, oxytocin and interoception
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“For example, OT receptors are concentrated in cholinergic brain regions regulating visual and auditory attention in nonhuman primates (6, 42, 43), consistent with the putative localization of OT receptors in human brain (44).”
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“This activation also encompassed basal forebrain regions rich in OT receptors (Loup et al., 1991), including the preoptic area, basal nucleus of Meynert, diagonal band of Broca, and lateral septum (supplementary Table 1, Fig.”
BackgroundDopaminergic-neuropeptide interactions in the social brain
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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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“Thus, while OXTR in VMH in rhesus macaques resembles the majority of mammalian species, there are some differences across primates.”
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- Authors
- Loup, F., Tribollet, E., Dubois-Dauphin, M., & Dreifuss, J. J.
- Corresponding author
- Dreifuss, J.J.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1991-08
- Volume
- 555
- Issue
- 2
- Pages
- 220-232
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2065752173
- Cited by
- 378
- References
- 62
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 11 · 2023: 6 · 2022: 8 · 2021: 21 · 2020: 33 · 2019: 20 · 2018: 18 · 2017: 22 · 2016: 23 · 2015: 21 · 2014: 22 · 2013: 29 · 2012: 17
- FWCI
- 5.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- oxytocin, vasopressin, receptor binding sites, human brain, lateral septal nucleus, thalamus, amygdala, basal forebrain, brainstem, hypothalamus, Alzheimer's disease, oxytocin antagonist
- MeSH terms
- Aged, Aged, 80 and over, Arginine Vasopressin, Autoradiography, Binding, Competitive, Brain, Brain Stem, Female, Humans, Hypothalamus, Male, Middle Aged, Oxytocin, Preoptic Area, Receptors, Angiotensin, Spinal Cord, Receptors, Vasopressin, Receptors, Oxytocin
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