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Young LJ, Wang Z. The neurobiology of pair bonding. Nat Neurosci 7: 1048-1054


Abstract and Figures

A neurobiological model for pair-bond formation has emerged from studies in monogamous rodents. The neuropeptides oxytocin and vasopressin contribute to the processing of social cues necessary for individual recognition. Mesolimbic dopamine is involved in reinforcement and reward learning. Concurrent activation of neuropeptide and dopamine receptors in the reward centers of the brain during mating results in a conditioned partner preference, observed as a pair bond. Differential regulation of neuropeptide receptor expression may explain species differences in the ability to form pair bonds. These and other studies discussed here have intriguing implications for the neurobiology of social attachment in our own species.
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Sexual attraction and the selective social attachments that often
follow are two of the most powerful driving forces of human behav-
ior, profoundly influencing art, music, literature and politics
throughout history. The presence of strong, enduring relationships
between sexual partners is widespread in nearly all societies, particu-
larly in societies where monogamy is a predominant feature of the
social organization. Whether humans have a biological propensity to
practice monogamy (or perhaps more correctly, serial monogamy) is
debatable; however, there is little doubt that the ability to form
intense social attachments—or pair bonds—with a mate has a biolog-
ical architecture with definable molecular and neural mechanisms.
Studies using monogamous rodents as models for social attachment
are providing insights into the biology of pair-bond formation.
The term ‘monogamy’ implies a social organization in which a
male and female mate exclusively with each other, although extra-
pair copulations are not unusual in monogamous species
.For this
reason, the term ‘monogamy’ is used here to refer to a social organi-
zation in which each member of a mating pair displays selective (but
not exclusive) affiliation and copulation, as well as nest sharing, with
the partner; it also typically implies biparental care of offspring.
Only 3–5% of mammals exhibit a monogamous social structure as
defined by these criteria
. One group of species in particular, voles in
the genus Microtus, has emerged as a valuable tool for investigating
the neurobiological mechanisms of pair-bond formation
.Here we
review recent discoveries concerning the molecular, cellular and neu-
robiological pathways that result in the development of a pair bond
in the monogamous prairie vole (Microtus ochrogaster). These stud-
ies provide a framework for understanding the regulation and evolu-
tion of complex social behavior and may provide insights into the
human social brain.
Peptidergic regulation of the pair bond
Like humans, voles display a remarkable diversity in social organiza-
tion. For example, prairie voles form enduring pair bonds and are
biparental, but montane (Microtus montanus) and meadow (Microtus
pennsylvanicus) voles are nonmonogamous and typically do not dis-
play biparental care
.In nature, the majority of prairie voles that
lose a mate never take on another partner
In the laboratory, researchers study pair-bond formation using a
partner-preference test. The testing apparatus consists of three cham-
bers connected by tubes. The ‘partner’ and a novel stranger’ are teth-
ered in their own chambers, whereas the subject is free to move
throughout the apparatus during a 3-h test. Pair bonding is inferred
when subjects spend significantly more time in close proximity to the
partner compared to the stranger (partner preference). In prairie
voles, mating facilitates formation of partner preference, although
cohabitation without mating may also result in partner-preference
formation under some circumstances
Two neuropeptides emerged initially as critical mediators of
partner-preference formation in prairie voles: oxytocin and arginine
vasopressin (AVP). Oxytocin also regulates mother-infant bonding
in sheep
,whereas AVP has been implicated in several male-typical
social behaviors, including aggression, scent marking and
.Infusion of oxytocin into the cerebral ventricles of
female prairie voles accelerates pair bonding, as these females require
only a brief cohabitation with a male, without mating, to form a
partner preference
. Likewise, central AVP infusion facilitates
pair-bond formation in male prairie voles without mating
Administration of selective oxytocin receptor (OTR) and AVP recep-
tor 1a (V1aR) antagonists prevents pair-bond formation in female
and male prairie voles, respectively
.Although both peptides may
facilitate pair-bond formation in either sex
,oxytocin seems to be
more important in females, whereas AVP is more critical in
.The mechanism underlying this sex difference in
behavioral response to oxytocin and AVP is unclear, because receptor
densities in the brain are similar in males and females. Early social
experience may also influence adult social behavior, as developmen-
tal studies suggest that neonatal oxytocin exposure enhances the like-
lihood of partner preference formation in adult male prairie voles
Although other factors, including stress and stress hormones, also
The neurobiology of pair bonding
Larry J Young
& Zuoxin Wang
A neurobiological model for pair-bond formation has emerged from studies in monogamous rodents. The neuropeptides oxytocin
and vasopressin contribute to the processing of social cues necessary for individual recognition. Mesolimbic dopamine is involved
in reinforcement and reward learning. Concurrent activation of neuropeptide and dopamine receptors in the reward centers of the
brain during mating results in a conditioned partner preference, observed as a pair bond. Differential regulation of neuropeptide
receptor expression may explain species differences in the ability to form pair bonds. These and other studies discussed here have
intriguing implications for the neurobiology of social attachment in our own species.
Center for Behavioral Neuroscience, Department of Psychiatry and
Behavioral Sciences, and Yerkes National Primate Research Center, Emory
University, Atlanta, Georgia 30322, USA.
Department of Psychology and
Program in Neuroscience, Florida State University, Tallahassee, Florida
32306, USA.
Correspondence should be addressed to L.J.Y. (
Published online 26 September 2004; doi:10.1038/nn1327
1048 VOLUME 7
© 2004 Nature Publishing Group
modulate partner-preference formation
,for the sake of clarity
we will restrict our focus to oxytocin and AVP, as well as their inter-
actions with other neurotransmitter systems.
The first hypotheses about the neuroanatomical basis of pair-
bond formation came from comparisons of OTR and V1aR distri-
butions in the brains of monogamous and nonmonogamous vole
species. Compared to nonmonogamous species, monogamous
prairie voles have higher densities of OTR in the caudate putamen
and nucleus accumbens (Fig. 1a,b)
and higher densities of V1aR
in the ventral pallidum, medial amygdala and mediodorsal thala-
mus (Fig. 1c,d)
.Some of these regions are involved in pair-bond
formation. For example, infusion of an OTR antagonist into the
prefrontal cortex and nucleus accumbens of females, but not the
caudate putamen, blocks mating-induced partner-preference
formation (Fig. 1e)
.In males before mating, blocking V1aR neu-
rotransmission in the ventral pallidum, but not the medial amyg-
dala or mediodorsal thalamus, also inhibits partner-preference
formation (Fig. 1f)
.Infusion of V1aR antagonist into the lateral
septum, which expresses some V1aR in both species, also prevents
mating-induced pair-bond formation in males
Sex, reward and pair bonding
Results from anatomical and pharmacological studies indicate that
the prefrontal cortex, nucleus accumbens and ventral pallidum are
all critical brain regions in pair-bond formation. These regions are
also involved in the mesolimbic dopamine reward system, suggest-
ing that pair-bond formation uses the same neural circuitry as
reward. Reward processing depends on the mesocorticolimbic
dopaminergic system consisting of dopamine neurons in the ventral
tegmental area and their projections to the nucleus accumbens, pre-
frontal cortex and other brain areas
.The ventral pallidum is a
major target of the nucleus accumbens
, and it further processes
and relays stimuli from the nucleus accumbens to mediate locomo-
tor responses to rewarding stimuli
.Dopamine release within
this circuit is critically involved in natural reward (food intake and
mating) as well as maladaptive (drug) reward
.Studies also
implicate this circuit in conditioned reward learning, such as drug-
induced place preferences
, in which neutral stimuli become asso-
ciated with rewarding stimuli.
Given that mating is rewarding in rodents
and facilitates pair-
bond formation in voles, some researchers have hypothesized that
pair bonding may be the result of conditioned reward learning, in
which an association forms between the reinforcing properties of sex
(unconditioned stimulus) and the specific olfactory signature of the
partner (conditioned stimulus)
.For example, both male and
female rats prefer to spend time in the chamber in which they copu-
lated (a conditioned place preference)
, and this sexual condition-
ing depends on D1-type and D2-type dopamine receptor activation
in the nucleus accumbens
Consistent with the hypothesis that pair bonding involves condi-
tioned learning, dopamine within the nucleus accumbens is critical
for partner preference formation in prairie voles (Fig. 2). The
nucleus accumbens in voles contains dopamine terminals and
receptors (Fig. 2b)
and mating results in an increase (51%) in
extracellular dopamine in the nucleus accumbens of females
(Fig. 2c)
.Mating also tends to increase dopamine turnover in the
nucleus accumbens of males
.Systemic administration, or local
injection into the nucleus accumbens, of haloperidol (a nonselective
dopamine receptor antagonist) blocks mating-induced partner
preferences, whereas apomorphine (a nonselective dopamine recep-
tor agonist) facilitates partner preference without mating in both
male and female prairie voles (Fig. 2a)
The dopaminergic regulation of pair-bond formation in the
nucleus accumbens is receptor subtype–specific: activation of D2, but
OCTOBER 2004 1049
Figure 1 OTR and V1aR regulation of pair bonding in prairie voles. (a,b) Monogamous prairie voles (a) have higher densities of OTR in the nucleus
accumbens (NAcc) and caudate putamen (CP) than do nonmonogamous montane voles (b). Both species have OTR in the prefrontal cortex (PFC).
(c,d) Male prairie voles (c) have higher densities of V1aR in the ventral pallidum (VP) than do montane voles (d). (e) A selective OTR antagonist (OTA)
infused bilaterally into the NAcc or PFC, but not the CP, blocks partner-preference formation in female prairie voles
. (f) Infusion of a selective V1aR
antagonist (V1aRA) into the VP, but not into the mediodorsal thalamus (MDthal) or medial amygdala (MeA), prevents mating-induced partner-preference
formation in male prairie voles
. Scale bar, 1 mm.
© 2004 Nature Publishing Group
the density of D1, but not D2, receptors in the nucleus accumbens. No
changes in dopamine receptor binding occur in other dopaminergic
brain areas, including the caudate putamen
.As D1 activation in the
nucleus accumbens prevents pair bonding in males
, this increase in
D1 receptor density may serve to prevent the formation of new pair
bonds, thereby maintaining the current pair bond and stabilizing the
monogamous social organization.
not D1, receptors in the nucleus accumbens of female prairie voles
accelerates partner preferences without mating, whereas blockade of
D2 receptors antagonizes this behavior (Fig. 2d)
.In males, D2
receptor activation also facilitates partner preference, but D1 receptor
activation blocks partner preferences induced by mating or by D2
receptor activation
.Male prairie voles that have mated and pair
bonded with a female for two weeks also show a significant increase in
Figure 3 Sagittal view of a prairie vole brain illustrating a proposed neural
circuit model for pair bonding. In this model, mating activates the VTA,
resulting in increased dopamine activity in the prefrontal cortex (PFC) and
nucleus accumbens (NAcc). Concurrently, olfactory signals from the mate
are transmitted via the olfactory bulb (OB) to the medial nucleus of the
amygdala (MeA). Oxytocin acts in the MeA, and AVP acts in the lateral
septum (LS) to facilitate olfactory learning and memory. Mating also
stimulates increased extracellular concentrations of oxytocin in the PFC and
NAcc of females, and of vasopressin in the ventral pallidum (VP) of males.
AVP fibers in the LS and VP originate from cell bodies in the MeA and
bed nucleus of the stria terminalis (not shown). The source of oxytocin
projections to the NAcc, MeA and PFC has not been defined (hence the
dotted line), but they most likely originate from some population of cell
bodies in the preoptic or hypothalamic area (POA/Hyp). Glutamatergic
projections from the PFC to the NAcc are thought to be important in
reinforcement and therefore potentially in pair bonding. The concurrent activation of the dopaminergic system and the oxytocin or AVP system in the NAcc
or VP potentially results in the development of a conditioned partner preference. The VP is a major output relay of the NAcc and modulates motor output in
response to reinforcing stimuli via projections to the mediodorsal thalamus (MdThal) and cortical and mesencephalic motor nuclei.
1050 VOLUME 7
Figure 2 Dopamine regulates pair bonding in female prairie voles. (a) Females injected intraperitoneally with saline or saline containing a D1 receptor
antagonist (D1-ant), but not a D2 antagonist (D2-ant), showed partner preferences after 24 h of cohabitation with mating, indicating the importance of D2
receptors in pair-bond formation
. (b) Photomicrographs of immunoreactive staining for tyrosine hydroxylase (TH) and dopamine transporter (DAT) as well
as autoradiographic binding for D1 and D2 dopamine receptors in the nucleus accumbens (NAcc) and caudate-putamen (CP) of the prairie vole brain.
Scale bar, 500 µm. (c) Estrus female voles that mated with a male showed a significant (51%) increase above the baseline in extracellular dopamine
concentration in NAcc
. (d) Intra-NAcc administration of a D2 antagonist (D2-ant) blocked mating-induced partner preferences
. (e) Intra-NAcc
administration of a D2 agonist (D2-ago) induced partner-preference formation after 6 h of cohabitation with a male in the absence of mating
. This
behavior was blocked by coadministration of either the D2 antagonist (D2-ant) or the oxytocin receptor antagonist (OTA), suggesting that concurrent
activation of both D2 and oxytocin receptors in NAcc is essential for pair-bond formation
Olfactory signals
Motor cortex
Motor nuclei
© 2004 Nature Publishing Group
Although mating-induced dopamine release in the nucleus accum-
bens is important for pair-bond formation in prairie voles, mating
also induces dopamine release in the nucleus accumbens of other
species of rodents, such as rats, which do not form pair bonds
Why then does dopamine induce pair bonding only in monogamous
prairie voles? The answer may lie in the interaction of the oxytocin,
AVP and dopamine systems within the reward circuitry.
In female prairie voles, administration of an OTR antagonist into
the nucleus accumbens blocks partner preferences induced by D2
receptor activation, whereas blockade of D2 receptors in the nucleus
accumbens prevents partner preference formation induced by oxy-
(Fig. 2e). These data indicate that dopamine and oxytocin are
not acting sequentially, but rather that concurrent activation of both
oxytocin and dopamine D2 receptors, and the interaction between
these two systems in the nucleus accumbens, are necessary for pair-
bond formation in females. Similar studies have not been done in
males, but given that the D2 receptors in nucleus accumbens
V1aR in the ventral pallidum
are important for pair bonding in
males, and that these two areas are interconnected
, it is likely that
the dopamine and AVP systems also interact in the nucleus accum-
bens–ventral pallidum circuitry to influence pair-bond formation in
males. The nature of the interaction of these
systems in voles is not clear. Studies on drug
tolerance and addiction suggest that these
neuropeptides may modulate the role of
dopamine in the reward circuitry
Furthermore, dopamine administration
induces central oxytocin release, whereas
oxytocin administration increases central
dopamine levels in the rat
.The interac-
tion may also be indirect, with concurrent
activation modulating downstream circuits
involved in olfactory learning and condition-
ing, for example.
A neurobiological model for pair bonding
How might the oxytocin, AVP and dopamine
systems interact to facilitate pair-bond for-
mation? There are now several studies sug-
gesting that both oxytocin and AVP are
involved in the neural processing of sensory
cues involved in social learning. In rodents,
both neuropeptides are implicated in the
processes required to identify the olfactory
signatures of conspecifics (social recogni-
.Oxytocin knockout mice fail to rec-
ognize individuals to which they have been
previously exposed
, and infusions of oxy-
tocin in the medial amygdala completely
restore social recognition in these mice
Selective V1aR antagonist or antisense V1aR
administered into the lateral septum of rats
also inhibits social recognition
infusion of AVP or overexpression of the
V1aR in this region enhances social recogni-
tion abilities
. V1aR knockout mice also
exhibit a complete loss of social recogni-
.However, both oxytocin and V1aR
knockout mice perform normally in other
olfactory and cognitive tasks, suggesting that
this deficit is specific for social discrimina-
.Given this role for oxytocin and AVP in social recognition
and the interaction of these peptides with mesolimbic dopamine, a
reasonable hypothesis is that pair bonding results from the conver-
gence of social discrimination circuits and the reinforcing properties
of the mesolimbic dopamine reward circuit (Fig. 3).
Mating in both males and females correlates with neural activity in
several brain regions, including the ventral tegmental area
(VTA), medial amygdala, preoptic area and hypothalamus
Dopaminergic projections from the VTA release dopamine in the
nucleus accumbens and prefrontal cortex, which has strong gluta-
matergic projections back to the nucleus accumbens
olfactory cues from the partner are processed by the main and acces-
sory olfactory bulbs, and subsequently by the medial amygdala and
lateral septum, which are critical for social recognition. The medial
amygdala and bed nucleus of the stria terminalis are major sources of
AVP fibers projecting to the ventral pallidum and lateral septum
whereas oxytocin fibers in the nucleus accumbens most likely origi-
nate from neurons in the preoptic area or hypothalamus
of these areas during mating may result in local release of these pep-
tides. Indeed, in vivo microdialysis shows that AVP is released in the
male prairie vole ventral pallidum during mating (J.C. Morales and
OCTOBER 2004 1051
Figure 4 The molecular genetics of pair bonding. (a) Male meadow voles overexpressing the V1aR
receptor in the ventral pallidum (V1aR-vp) showed enhanced mating-induced partner preferences
compared to control animals (Ctrl all). Infusion of a D2 receptor antagonist (D2-ant) before mating
abolished the partner preference in these males (V1aR-vp + D2-ant)
. (b) V1aR binding autoradiograms
illustrating the increased expression of V1aR in the ventral pallidum (vp) in experimental males
compared to control animals. (c) The structure of the Avpr1a gene of prairie and montane voles. The
gene is highly homologous except for an expanded microsatellite sequence in the 5flanking region of
the prairie vole gene. Yellow boxes indicate coding regions with the black bars representing the seven
transmembrane domains. Gray indicates untranslated regions. The green and red boxes indicate
the relative length and position of the microsatellite sequences in the montane and prairie vole
genes, respectively. (d) The effect of the microsatellite sequence on expression as determined by
a transcription reporter assay. The prairie vole promoter was spliced upstream of firefly luciferase.
Exchanging only the prairie vole microsatellite sequence (prairie MS) with the montane vole sequence
(montane MS) resulted in a significant alteration in luciferase expression in a rat A7r5 cell line.
© 2004 Nature Publishing Group
L.J.Y., unpublished data), and vaginocervical stimulation increases
central oxytocin release in sheep
.Thus, mating ultimately results in
the concurrent activation of D2 receptors in the nucleus accumbens
of both sexes, OTR in the prefrontal cortex and nucleus accumbens of
females and V1aR in the ventral pallidum of males. As a result, the
reinforcing, hedonic properties of mating may become coupled with
the olfactory signatures of the mate, resulting in a conditioned part-
ner preference, much in the same way as drugs of abuse result in con-
ditioned place preferences. In this model, the basic mechanism of
bonding is similar in males and females; the neuropeptides are simply
modulating two different nodes of the same circuits. In nonmonoga-
mous species, sexual activity can also result in conditioned prefer-
ences for nonsocial stimuli, including neutral odors placed on
the sexual partner
.However, in nonmonogamous species, the
dopamine system and the oxytocin and AVP systems are uncoupled
because of the low densities of OTR and V1aR in this pathway.
We must stress that the study of the neurobiology of social bonding
in voles is in its infancy, and the model described here draws heavily
on neuroanatomical, behavioral and pharmacological data obtained
from rat studies, particularly those focusing on conditioned learning,
reinforcement and addiction. Our model is clearly limited in scope,
and raises many more questions than it answers. For example, what is
the nature of the interactions between the peptide and dopamine sys-
tems? How are other neurotransmitters such as glutamate and GABA
involved in pair bonding? How do the circuits involved in olfactory
processing converge on the reward circuits, and how does this result
in olfactory conditioning? Is there a role for other structures such as
the hippocampus and cortex? And finally, what types of molecular
and synaptic changes take place to lead to the development of a per-
manent pair bond. Thus, although this admittedly is an oversimpli-
fied model, it provides a neurobiological framework in which to
generate and test hypotheses regarding pair bonding.
The molecular basis of the pair bond
If our current model is correct, one would predict that pair-bond-
ing behavior could be potentially induced in a nonmonogamous
species by expressing OTR or V1aR in the nucleus accumbens or
ventral pallidum. We tested this prediction using viral
vector–mediated gene transfer to overexpress Avpr1a, the gene
encoding V1aR, in the ventral pallidum of the nonmonogamous
male meadow vole
(Fig. 4a,b). After cohabitation with a receptive
female during which copulation occurred, these transgenic animals
showed enhanced partner preference compared to controls.
Pretreating virus-treated voles with a D2 receptor antagonist pre-
vented partner preferences (Fig. 4a). This study has remarkable
implications for the evolution of complex behavior, suggesting that
mutations altering the expression pattern of a single gene can have
a profound impact on complex social behaviors.
How did the differential patterns of V1aR and OTR expression
emerge between monogamous and nonmonogamous species?
Because researchers have studied this question most extensively
with respect to Avpr1a,we will limit our discussion to this gene. The
Avpr1a genes in the prairie vole and nonmonogamous montane vole
are highly homologous
.However, approximately 660 base pairs
upstream of the transcription start site, the prairie vole Avpr1a gene
contains 500 base pairs of highly repetitive sequence, known as a
microsatellite; in montane and meadow voles, this repetitive
sequence is much shorter (Fig. 4c). Microsatellite sequences are
highly unstable
, and there are several examples of genes for which
polymorphic microsatellites in the regulatory region result in differ-
ential levels of expression
.It is clear that the sequences proximal
to the Avpr1a coding region determine the pattern of expression, as
a transgenic mouse expressing a prairie vole Avpr1a gene that
included 2.4 kb of upstream sequence expressed the Avpr1a gene in
a pattern similar to that of the prairie vole
.The species-specific
microsatellite also modulates gene expression in a cell type–specific
manner. Replacing the prairie vole microsatellite with the shorter
montane vole sequence increases reporter gene expression in a tran-
scription reporter assay (Fig. 4d)
.Although the results, obtained
in a cultured rat A7r5 cell line, are in the opposite direction from
what one would predict from the species differences in ventral palli-
dal receptor binding, the effect is consistent with the higher level of
V1aR expression in the septum of montane voles compared to
prairie voles. As the effect of the microsatellite on expression is cell
type–specific, it is likely that in other cell lines, and indeed in the
brain itself, the prairie vole microsatellite might yield higher levels
of transcription than the montane vole sequence. Together, these
data suggest that expansion or contraction of this microsatellite in
the 5 flanking regulatory region of this gene could have been the
molecular event that resulted in the altered expression of the V1aR
gene in the preexisting reward circuit, resulting in the biological
potential to develop conditioned partner preferences. We do not
know, however, which selective pressures influenced the frequency
of the microsatellite alleles, and consequently the monogamous
social structure, in voles. The human V1aR gene (AVPR1A) has
three highly polymorphic microsatellite sequences in the 5flanking
region, and it has been suggested that variation in one of these
sequences may be associated with autism
Implications for human bonding
Undoubtedly there are numerous molecular and neurobiological
pathways that could evolve to support pair-bond formation between
mates, and different species may have achieved similar behaviors
through a process of convergent evolution involving different circuits.
We strongly emphasize that there are no hard data demonstrating
common physiological mechanisms for pair-bond formation in voles
and man. In addition, as with many human behaviors, the emergence
of the neocortex and its ability to modify subcortical function cannot
be ignored. Nevertheless, it is intriguing to consider the possibility
that similar mechanisms may underlie the formation of pair bonds in
both humans and rodents. Although it is not known whether human
sexual intercourse results in central oxytocin or AVP release, plasma
oxytocin levels are elevated at the time of orgasm in women, and sim-
ilarly, plasma AVP concentrations increase during sexual arousal in
.These changes may or may not reflect central peptide
release; it is intriguing, however, to consider how aspects of human
sexuality may reflect the influence of intercourse on pair bonding. For
example, human females are ‘hidden ovulators’ and engage in sexual
activity throughout the ovarian cycle. This regular sexual activity may
serve to activate the circuits underlying bonding, thus strengthening
the pair bond. Furthermore, in contrast to other mammalian species,
human females have enlarged mammary tissues independent of lacta-
tion, and breast and nipple stimulation are an integral part of human
sexuality. Nipple stimulation during lactation is one of the most
potent stimuli for oxytocin release
.Ifoxytocin is involved in human
social attachment, this aspect of sexual activity may thus serve to rein-
force sexual bonding.
Human imaging studies also provide evidence consistent with the
hypothesis that reward and neuropeptide circuits are involved in pair
bonding in humans. When human subjects viewed photographs of
individuals with whom they claimed to be romantically in love, their
brain activity patterns (as measured by functional magnetic reso-
1052 VOLUME 7
© 2004 Nature Publishing Group
nance imaging, fMRI) looked remarkably similar to those observed
after cocaine or µ-opioid infusions, with heavy activation of the VTA
and striatal dopamine regions
.Many of the regions activated are
rich in oxytocin, AVP or their respective receptors
.Similar pat-
terns of activity occur when mothers view images of their own chil-
dren, suggesting some overlap between the neural mechanisms of
maternal attachment and those of romantic love
.In addition, the
VTA and striatum show substantial activity (as measured by positron
emission tomography, PET) during ejaculation in men, paralleling
the activation pattern evoked by a heroin rush
The work reviewed here has focused primarily on the neurobiology
of mating-induced, heterosexual pair bonds. It is also intriguing to
consider whether other types of social bonds, including familial
bonds, close friendships or homosexual relationships might use some
of the same neurobiological mechanisms.
The pair bond is an integral aspect of human sexuality with
important implications for both psychological and physical health.
In the last few years, the neurobiological mechanisms underlying
pair bonding in voles have provided valuable insights into the social
brain. The convergence of mechanisms underlying reward, condi-
tioning and the neural processing of social cues seems to result in the
motivation to maintain selective contact with one’s partner. It is
unclear whether the same mechanisms are involved in rodent and
human pair bonding, but it is likely that in both cases, the social
brain and reward circuits are both involved, perhaps giving credence
to the adage,“love is an addiction.
The authors acknowledge A.Z. Murphy, E.A.D. Hammock, M.M. Lim, B. Aragona and
T. Curtis for discussion and comments during the writing of this manuscript. The
authors especially thank C.S. Carter and T.R. Insel for their pioneering work, which
laid the foundation for neurobiological studies of social bonding. Much of this work
was supported by National Institute of Mental Health grants to L.J.Y. and Z.X.W.
The authors declare that they have no competing financial interests.
Received 23 June; accepted 10 August 2004
Published online at
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... However, animal studies provide strong evidence for such a relationship (Acevedo et al., 2012). For example, Young and Wang considered a special worth for the function of brain structures that implement the production and reception of dopamine for pair bonding, revealing sex differences in the relationship at the same time (Young and Wang, 2004). Subsequently, these findings were partially confirmed in a neuroimaging study in humans: the passionate stage of romantic love is accompanied by a pronounced activation of the dopaminergic system in two regions, the medial orbitofrontal cortex and medial prefrontal cortex (Takahashi et al., 2015). ...
... As mentioned previously, ethnicity is very important for assessing the role of the dopaminergic system (Pearce et al., 2018a). Young and Wang (2004) emphasized the critical role of the function of brain structures that implement neurotransmitter production and reception for pair bonding, while emphasizing the sex differences simultaneously. At the same time, overly restricted samples invariably lead to limited conclusions that are valid only for narrow social groups (Lavner and Bradbury, 2010). ...
Full-text available
Introduction: Couples’ relationships defined by a complex interaction between the two partners and their intrapersonal traits. Romantic; relationships and love are associated with marital satisfaction and stability, as well as couples’ happiness and health. Personality traits influence romantic relationships and, personality influenced by genetical and non-genetically factors. The roles of non-genetically factors such as socioeconomic position and external appearance have revealed in determining the quality of romantic relationships. Methods: We; performed a scoping systematic review to assess the association between genetics and epigenetic factors and romantic relationship. Relevant articles were identified by PubMed, EMBASE, Web of Science, Scopus, and the APA PsycInfo searching between inception and 4 June 2022. Results: Different studies evaluated the associated polymorphisms in 15 different genes or chromosomal regions. In the first step; we classified them into four groups: (1) Oxytocin-related signaling pathway ( OXTR , CD38 , and AVPR1A ); (2) Serotonin-related signaling pathway ( SLC6A4 , HTR1A , and HTR2A ); (3) Dopamine and catecholamine-related signaling pathway ( DRD1 , DRD2 , DRD4 , ANKK1 , and COMT ); and (4) other genes ( HLA , GABRA2 , OPRM1 , and Y-DNA haplogroup D-M55). Then, we evaluated and extracted significant polymorphisms that affect couple adjustment and romantic relationships. Discussion: Overall, the findings suggest that genetic and epigenetics variants play a key role in marital adjustment and romantic relationships over time.
... A highly variable regional distribution of OXTR is observed in mammals, even between closely-related species (Walum and Young, 2018), originally described in the prairie and montane voles, where different OXTR distributions relate to striking differences in social behavior (Insel and Shapiro, 1992;Young and Wang, 2004). Region-specific sex differences have also been reported in different species including mice (Hammock and Levitt, 2013;Sharma et al., 2019;Newmaster et al., 2020). ...
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The neurohormone oxytocin (OXT) has been implicated in the regulation of social behavior and is intensively investigated as a potential therapeutic treatment in neurodevelopmental disorders characterized by social deficits. In the Magel2-knockout (KO) mouse, a model of Schaaf-Yang Syndrome, an early postnatal administration of OXT rescued autistic-like behavior and cognition at adulthood, making this model relevant for understanding the actions of OXT in (re)programming postnatal brain development. The oxytocin receptor (OXTR), the main brain target of OXT, was dysregulated in the hippocampus of Magel2-KO adult males, and normalized upon OXT treatment at birth. Here we have analyzed male and female Magel2-KO brains at postnatal day 8 (P8) and at postnatal day 90 (P90), investigating age, genotype and OXT treatment effects on OXTR levels in several regions of the brain. We found that, at P8, male and female Magel2-KOs displayed a widespread, substantial, down-regulation of OXTR levels compared to wild type (WT) animals. Most intriguingly, the postnatal OXT treatment did not affect Magel2-KO OXTR levels at P8 and, consistently, did not rescue the ultrasonic vocalization deficits observed at this age. On the contrary, the postnatal OXT treatment reduced OXTR levels at P90 in male Magel2-KO in a region-specific way, restoring normal OXTR levels in regions where the Magel2-KO OXTR was upregulated (central amygdala, hippocampus and piriform cortex). Interestingly, Magel2-KO females, previously shown to lack the social deficits observed in Magel2-KO males, were characterized by a different trend in receptor expression compared to males; as a result, the dimorphic expression of OXTR observed in WT animals, with higher OXTR expression observed in females, was abolished in Magel2-KO mice. In conclusion, our data indicate that in Magel2-KO mice, OXTRs undergo region-specific modifications related to age, sex and postnatal OXT treatment. These results are instrumental to design precisely-timed OXT-based therapeutic strategies that, by acting at specific brain regions, could modify the outcome of social deficits in Schaaf-Yang Syndrome patients.
... Abnormal OT-DA interactions may contribute to behavioral disorders such as autism, sexual dysfunction, addiction and depression, and risk for post-traumatic stress disorders [21,48]. The OT-mediated social affiliative behaviors seem linked to regulation of the dopaminergic reward system [49,50]. So, it is perhaps not surprising that the dopaminergic system is involved in the mechanism(s) underlying the effect of OT in modulating addictive-related behaviors [51]. ...
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Abstract: The ability of oxytocin (OT) to interact with the dopaminergic system through facilitatory D2-OT receptor (OTR) receptor-receptor interaction in the limbic system is increasingly considered to play roles in social or emotional behavior, and suggested to serve as a potential therapeutic target. Although roles of astrocytes in the modulatory effects of OT and dopamine in the central nervous system are well recognized, the possibility of D2-OTR receptor-receptor interaction in astrocytes has been neglected. In purified astrocyte processes from adult rat striatum, we assessed OTR and dopamine D2 receptor expression by confocal analysis. The effects of activation of these receptors were evaluated in the processes through a neurochemical study of glutamate release evoked by 4-aminopyridine; D2-OTR heteromerization was assessed by co-immunoprecipitation and proximity ligation assay (PLA). The structure of the possible D2-OTR heterodimer was estimated by a bioinformatic approach. We found that both D2 and OTR were expressed on the same astrocyte processes and controlled the release of glutamate, showing a facilitatory receptor-receptor interaction in the D2-OTR heteromers. Biochemical and biophysical evidence confirmed D2-OTR heterodimers on striatal astrocytes. The residues in the transmembrane domains four and five of both receptors are predicted to be mainly involved in the heteromerization. In conclusion, roles for astrocytic D2-OTR in the control of glutamatergic synapse functioning through modulation of astrocytic glutamate release should be taken into consideration when considering interactions between oxytocinergic and dopaminergic systems in striatum.
... Des données récentes mettent également en avant l'importance des modifications neurotrophiques cérébrales, notamment hippocampiques (Young et Wang 2004). Au regard du rôle des facteurs neurotrophiques, dont le BDNF, dans la vulnérabilité à la dépression en préclinique (Hillerer et al. 2014;Duman et Monteggia 2006), dans la vulnérabilité aux troubles de l'humeur en clinique (Wichers et al. 2008;Corwin et Pajer 2008), des études assez récentes se sont attachées à étudier les relations entre les neurotrophines et le risque de DPN. ...
Pre and postnatal phases are thought to be associated with physiological, biological, et psychical upheavals. The perinatal period constitutes a time of psychical vunerability during which women are at risk of developping a mental illness.Postpartum depression (PPD) forms one of the major complications of postpartum and affects 20% of women. It's considered to be one of the great model of chronic stress.This thesis' main aim is to study the physiopathological mechanisms inducing the emergence of a PPD, with the help of psychological, physiopathological, biological and genetical measures of pregnancy monitoring. More precisely, we want to identify a predictive value for the emergence of PPD by evaluating if the mindfulness disposition is a protecting factor in the occurence of PPD.Indeed, numerous studies have shown that mindfulness is an asset for overall health, especially in the scope of stress prevention and its consequences.Results underline the protective role of the mindfulness functioning on the risk of PPD occurence. Psychological factors linked with mood and perceived social support are also suggested for pregnancy monitoring.Concomitantly, we've sought to evaluate the perinatal healthcare providers' scope of knowledge of post-partum psychical complications, especially on PPD. The results highlight that these professionals are poorly trained in the identification and management of these complications and there are a number of personal and organizational obstacles to this observation.Considering these results, we've proposed preventing counter measures of PPD by targeting pregnant women and perinatal health providers.In this context, we've started the inception of a training tool for healthcare providers in order to assist them in better prevention, screening and undertaking one of the gravest psychical complications of PPD, with the help of Virtual Reality environment. This thesis work is part of the current consideration of the deleterious consequences of PND on the family unit and on the development of the child.
The neuropeptide arginine-vasopressin (AVP) is well known for its peripheral effects on blood pressure and antidiuresis. However, AVP also modulates various social and anxiety-related behaviors by its actions in the brain, often sex-specifically, with effects typically being stronger in males than in females. AVP in the nervous system originates from several distinct sources which are, in turn, regulated by different inputs and regulatory factors. Based on both direct and indirect evidence, we can begin to define the specific role of AVP cell populations in social behavior, such as, social recognition, affiliation, pair bonding, parental behavior, mate competition, aggression, and social stress. Sex differences in function may be apparent in both sexually-dimorphic structures as well as ones without prominent structural differences within the hypothalamus. The understanding of how AVP systems are organized and function may ultimately lead to better therapeutic interventions for psychiatric disorders characterized by social deficits.
Oxytocin is a pleiotropic molecule which, in addition to its facilitating action during parturition and milk ejection, is involved in social and prosocial behaviors such as attachment. This article presents, after a brief historical review, the action of oxytocin during the milk ejection reflex. Oxytocin is indeed essential for this vital function in mammals. It is both a neurohormone released into the bloodstream by the axon terminals of the posterior pituitary and a neuromodulator released in the hypothalamus by the soma and dendrites of oxytocinergic magnocellular neurons. In addition, oxytocin is also released by the axon terminals of parvocellular neurons and axon collaterals of magnocellular neurons in the brain. Both maternal attachment in rats and ewes and attachment between sexual partners in the prairie vole, one of the few monogamous rodent species, are mediated by central oxytocin. However, neither administering oxytocin into the brain nor increasing expression of the oxytocin receptor in the nucleus accumbens using a gene transfer technique converts polygamous voles to monogamous ones. Unfortunately, translation of animal data to human remains problematic due to still unsolved difficulties in modifying the level of oxytocin in the brain.
Full-text available
The neuropeptide oxytocin has been in the focus of scientists for decades due to its profound and pleiotropic effects on physiology, activity of neuronal circuits and behaviors. Until recently, it was believed that oxytocinergic action exclusively occurs through direct activation of neuronal oxytocin receptors. However, several studies demonstrated the existence and functional relevance of astroglial oxytocin receptors in various brain regions in the mouse and rat brain. Astrocytic signaling and activity are critical for many important physiological processes including metabolism, neurotransmitter clearance from the synaptic cleft and integrated brain functions. While it can be speculated that oxytocinergic action on astrocytes predominantly facilitates neuromodulation via the release of gliotransmitters, the precise role of astrocytic oxytocin receptors remains elusive. In this review, we discuss the latest studies on the interaction between the oxytocinergic system and astrocytes, and give details of underlying intracellular cascades.
Historical evidence from stimulation and lesion studies in animals and humans demonstrated a close association between the hypothalamus and typical and atypical socioemotional behavior. A central hypothalamic contribution to regulation of socioemotional responses was also provided indirectly by studies on oxytocin and arginine vasopressin. However, a limited number of studies have so far directly investigated the contribution of the hypothalamus in human socioemotional behavior. To reconsider the functional role of the evolutionarily conserved hypothalamic region in regulating human social behavior, here I provide a synthesis of neuroimaging investigations showing that the hypothalamus is involved in multiple and diverse facets of human socioemotional behavior through widespread functional interactions with other cortical and subcortical regions. These neuroimaging findings are then integrated with recent optogenetics studies in animals demonstrating that the hypothalamus plays a more active role in eliciting socioemotional responses and is not simply a downstream effector of higher-level brain systems. Building on the aforementioned evidence, the hypothalamus is argued to substantially contribute to a continuum of human socioemotional behaviors promoting survival and preservation of the species that extends from exploratory and approaching responses facilitating social bonding to aggressive and avoidance responses aimed to protect and defend formed relationships.
Myths, drama, and sacred texts have warned against the fragile nature of human love; the closer the affiliative bond, the quicker it can turn into hatred, suggesting similarities in the neurobiological underpinnings of love and hatred. Here, I offer a theoretical account on the neurobiology of hatred based on our model on the biology of human attachments and its three foundations; the oxytocin system, the "affiliative brain", comprising the neural network sustaining attachment, and biobehavioral synchrony, the process by which humans create a coupled biology through coordinated action. These systems mature in mammals in the context of the mother‐infant bond and then transfer to support life within social groups. During this transition, they partition to support affiliation and solidarity to one's group and fear and hatred toward out‐group based on minor variations in social behavior. I present the Tools of Dialogue© intervention for outgroup members based on social synchrony. Applied to Israeli and Palestinian youth and implementing RCT, we measured social behavior, attitudes, hormones, and social brain response before and after the 8‐session intervention. Youth receiving the intervention increased reciprocity and reduced hostile behavior toward outgroup, attenuated the neural marker of prejudice and increased neural empathic response, reduced cortisol and elevated oxytocin, and adapted attitudes of compromise. These neural changes predicted peacebuilding support 7 years later, when young adults can engage in civil responsibilities. Our intervention, the first to show long‐term effects of inter‐group intervention on brain and behavior, demonstrates how social synchrony can tilt the neurobiology of hatred toward the pole of affiliation.
Oxytocin (OT) knock-out mice fail to recognize familiar conspecifics after repeated social exposures, despite normal olfactory and spatial learning abilities. OT treatment fully restores social recognition. Here we demonstrate that OT acts in the medial amygdala during the initial exposure to facilitate social recognition. OT given before, but not after, the initial encounter restores social recognition in OT knock-out mice. Using c-Fos immunoreactivity (Fos-IR) as a marker of neuronal activation in this initial encounter, we found similar neuronal activation in the wild-type (WT) and OT knock-out mouse in olfactory bulbs, piriform cortex, cortical amygdala, and the lateral septum. Wild-type, but not OT knock-out mice exhibited an induction of Fos-IR in the medial amygdala. Projections sites of the medial amygdala also failed to show a Fos-IR induction in the OT knock-out mice. OT knock-out, but not WT, mice showed dramatic increases in Fos-IR in the somatosensory cortex and the hippocampus, suggesting alternative processing of social cues in these animals. With site-specific injections of OT and an OT antagonist, we demonstrate that OT receptor activation in the medial amygdala is both necessary and sufficient for social recognition in the mouse.
This rodent forms social groups that appear to have evolved as an adaptation for living in a low-food habitat.
This chapter summarizes the available literature on parental behavior in voles. An attempt is also made to examine the interactions of the environment with the behavior, as well as to explore the possible neural mechanisms underlying parental care in voles. The chapter focuses on monogamous prairie (Microtus ochrogaster), pine (M. pinetorum) voles, promiscuous meadow (M. pennsylvanicus), and montane (M. montunus) voles because most of the work has been done on these species. Monogamous species with biparental care have provided useful models for studying the role of the father and juveniles in the care and development of pups. Voles have also provided excellent model systems for studying the neurobiological basis of parental care. Although this work is still very recent, the data from several sources suggest that specific brain areas—the medial preoptic area, the amygdala, and the lateral septum are important for various aspects of affiliation, including parental care. Two neuropeptide hormones, vasopressin (AVP) and oxytocin (OT), with pathways in these brain regions appear to influence pair bonding and parental care in prairie voles. AVP in the lateral septum appears especially important for paternal care; OT (possibly in the amygdala) may influence maternal behavior. Exactly how and where these neuropeptides affect behavior remains to be defined, as does their roles in the nonmonogamous vole species.
The neuropeptide oxytocin has been implicated in the mediation of several forms of affiliative behavior including parental care, grooming, and sex behavior. Here we demonstrate that species from the genus Microtus (voles) selected for differences in social affiliation show contrasting patterns of oxytocin receptor expression in brain. By in vitro receptor autoradiography with an iodinated oxytocin analogue, specific binding to brain oxytocin receptors was observed in both the monogamous prairie vole (Microtus ochrogaster) and the polygamous montane vole (Microtus montanus). In the prairie vole, oxytocin receptor density was highest in the prelimbic cortex, bed nucleus of the stria terminalis, nucleus accumbens, midline nuclei of the thalamus, and the lateral aspects of the amygdala. These brain areas showed little binding in the montane vole, in which oxytocin receptors were localized to the lateral septum, ventromedial nucleus of the hypothalamus, and cortical nucleus of the amygdala. Similar differences in brain oxytocin receptor distribution were observed in two additional species, the monogamous pine vole (Microtus pinetorum) and the polygamous meadow vole (Microtus pennsylvanicus). Receptor distributions for two other neurotransmitter systems implicated in the mediation of social behavior, benzodiazepines, and mu-opioids did not show comparable species differences. Furthermore, in the montane vole, which shows little affiliative behavior except during the postpartum period, brain oxytocin receptor distribution changed within 24 hr of parturition, concurrent with the onset of maternal behavior. We suggest that variable expression of the oxytocin receptor in brain may be an important mechanism in evolution of species-typical differences in social bonding and affiliative behavior.
The prairie vole ( Microtus ochrogaster ), a monogamous rodent that forms long-lasting pair bonds, has proven useful for the neurobiological study of social attachment. In the laboratory, pair bonds can be assessed by testing for a partner preference, a choice test in which pair-bonded voles regularly prefer their partner to a conspecific stranger. Studies reported here investigate the role of dopamine D2-like receptors (i.e., D2, D3, and D4 receptors) in the nucleus accumbens (NAcc) for the formation of a partner preference in female voles. Mating facilitated partner preference formation and associated with an approximately 50% increase in extracellular dopamine in the NAcc. Microinjection of the D2 antagonist eticlopride into the NAcc (but not the prelimbic cortex) blocked the formation of a partner preference in mating voles, whereas the D2 agonist quinpirole facilitated formation of a partner preference in the absence of mating. Taken together, these results suggest that D2-like receptors in the NAcc are important for the mediation of social attachments in female voles. (PsycINFO Database Record (c) 2012 APA, all rights reserved)