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The Journal of Neuroscience, September 15, 2001, 21(18):7392-7396
Facilitation of Affiliation and Pair-Bond Formation by
Vasopressin Receptor Gene Transfer into the Ventral Forebrain of a
Monogamous Vole
Lauren J.
Pitkow1,
Catherine A.
Sharer1,
Xianglin
Ren2,
Thomas R.
Insel1,
Ernest F.
Terwilliger2, and
Larry J.
Young1
1 Center for Behavioral Neuroscience and Department of
Psychiatry, Emory University, Atlanta, Georgia 30322, and
2 Harvard Institutes of Medicine and Beth Israel Deaconess
Medical Center, Boston, Massachusetts 02215
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ABSTRACT |
Behaviors associated with monogamy, including pair-bond formation,
are facilitated by the neuropeptide vasopressin and are prevented by a
vasopressin receptor [V1a receptor (V1aR)] antagonist in the male
prairie vole. The neuroanatomical distribution of V1aR dramatically
differs between monogamous and nonmonogamous species. V1aR binding is
denser in the ventral pallidal region of several unrelated monogamous
species compared with nonmonogamous species. Because the ventral
pallidum is involved in reinforcement and addiction, we hypothesize
that V1aR activation in this region promotes pair-bond formation via a
mechanism similar to conditioning. Using an adeno-associated viral
vector to deliver the V1aR gene, we increased the
density of V1aR binding in the ventral pallial region of male prairie
voles. These males exhibited increased levels of both anxiety and
affiliative behavior compared with control males. In addition, males
overexpressing the V1aR in the ventral pallidal region, but not control
males, formed strong partner preferences after an overnight
cohabitation, without mating, with a female. These data demonstrate a
role for ventral pallidal V1aR in affiliation and social attachment and
provide a potential molecular mechanism for species differences in
social organization.
Key words:
vasopressin; V1a receptor; ventral pallidum; social
attachment; affiliation; viral vector; monogamy; pair bond
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INTRODUCTION |
Affiliative behavior and social
bonding are essential components of human society, yet little is known
of the neural circuitry regulating these complex behavioral processes.
Disruptions in these processes may be associated with psychiatric
diseases characterized by social deficits, such as autism. Voles
provide a useful animal model for investigating the neural mechanisms
underlying these behaviors (Carter, 1998 ; Young et al., 1998; Insel and
Young, 2001). Vole species display a wide range of social behavior,
ranging from being highly social and monogamous to being solitary and promiscuous. Both field and laboratory studies have demonstrated that
prairie voles (Microtus ochrogaster) are a highly gregarious species that forms enduring, selective social bonds between mates (Shapiro and Dewsbury, 1990; Carter and Getz, 1993).
Pharmacological studies in prairie vole males have demonstrated that
the neuropeptide arginine vasopressin (AVP) increases affiliative
behavior and is critical for the formation of the pair bond (Winslow et
al., 1993; Cho et al., 1999; Young et al., 1999a). In the laboratory,
the formation of the pair bond is assessed using a partner-preference
paradigm in which the subject chooses to associate with either the
partner or a novel female of similar stimulus value. An AVP antagonist
selective for the V1a receptor (V1aR) subtype blocks the development of
the partner preference when given centrally before mating (Winslow et
al., 1993; Cho et al., 1999). Conversely, central infusions of AVP
facilitate partner-preference formation even in the absence of mating
(Winslow et al., 1993). AVP infusions do not alter affiliative behavior in the nonmonogamous montane vole (Young et al., 1999a). These data
suggest that AVP released during social interactions and during mating
bouts activates neural circuitry that regulates these behaviors in a
species-specific manner.
The neuroanatomical distribution of the V1aR differs dramatically among
closely related species that differ in their social structure,
providing a potential explanation for the species-specific effects of
AVP (Insel et al., 1994). The monogamous prairie (Microtus ochrogaster) and pine (M. pinetorum) voles, California
mouse (Peromyscus californicus), and common marmoset
(Callithrix jacchus) each have high densities of V1aR
binding in a region of the ventral forebrain containing the ventral
pallidum and substantia innominata. In this same region, relatively
little V1aR binding is detectable in related nonmonogamous montane
(M. montanus) and meadow (M. pennsylvanicus)
voles, white-footed mice (Peromyscus leucopus), and rhesus
monkeys (Insel et al., 1994; Bester-Meredith et al., 1999; Young, 1999;
Young et al., 1999b).
Because the ventral pallidum has been associated with reward and
conditioned place preference (McBride et al., 1999), we hypothesized that V1aR in this area may facilitate affiliation and
partner-preference formation through its reinforcing actions in the
ventral pallidum. If this is correct, animals with high densities of
V1aR in this region would exhibit higher levels of affiliative behavior
and be more likely to form social attachments. To test this hypothesis, we used an adeno-associated viral (AAV) vector to selectively increase V1aR expression in the ventral pallidal area of male prairie
voles and examined the behavioral consequences, including anxiety,
affiliation, and partner-preference formation.
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MATERIALS AND METHODS |
Animals and treatment
Subjects were 2- to 5-month-old sexually naive male prairie
voles (M. ochrogaster) reared in our laboratory from
field-caught specimens. Animals were housed with one to two same-sex
litter mates in a 14/10 hr light/dark cycle and were provided food
(Purina Rabbit Chow; Purina Mills, St. Louis, MO) and water
ad libitum. Littermates housed together were assigned to
different treatment groups to control for variability within litters
and within cages. All experiments were performed in compliance with the
rules and oversight of the Emory Institutional Animal Care and Use Committee.
Three groups of male prairie voles were used in this study. The
experimental group [V1aR-ventral pallidum (VP);
n = 13] received bilateral infusions of the
neuron-specific enolase (NSE)-prairie vole V1aR
(pvV1aR) viral vector into the ventral pallidal area. One
control group [V1aR-caudate putamen (CP); n = 9] received identical injections into the caudate putamen, a region
that does not express the endogenous V1aR. A second control group
(lacZ-VP/CP, n = 8) received a
control vector expressing the lacZ gene rather the
V1aR, into either the ventral pallidum or the caudate putamen.
AAV infusions were performed under ketamine anesthesia in a stereotaxic
apparatus fitted with an Ultra Micro Pump II (World Precision
Instruments, Sarasota, FL) apparatus with a Hamilton syringe adapter.
The injection coordinates were as follows (in mm): ventral
pallidum, 1.3 anterior, 1.0 lateral, and 5.5 ventral; caudate putamen,
1.3 anterior, 2.0 lateral, and 4.0 ventral. Bregma was used as the
anterior-posterior and medial-lateral reference point, and the top of
the skull at the anterior-lateral coordinate site was used as the
dorsal-ventral reference point. Once the Hamilton syringe was lowered
to the injection site, the recombinant AAV (rAAV) preparation (1 µl/side at 108 infectious units/µl)
was infused at a rate of 3-5 nl/sec. The needle was left in
place for 2 min after the injection. All injections were bilateral.
Animals recovered for 12 d before behavioral testing.
After the behavioral studies, brains were collected and analyzed for
V1aR expression and accuracy of injection.
AAV production
The prairie vole V1aR viral vector
(NSE-pvV1aR) consisted of a modified V1aR
genomic clone with the majority of the intron removed, spliced
downstream of a neuron-specific enolase promoter (Fig.
1). The V1aR cassette was
created by first excising the sequence downstream of the
HindIII site located 123 bp 3' of the exon-intron boundary.
The HindIII end was destroyed and the plasmid was
recircularized to facilitate subsequent cloning steps. The second exon
was amplified by PCR using a 5' primer located 133 bp upstream of the
second exon and a 3' primer that contained the stop codon and a
HindIII restriction site. The amplified fragment was spliced
downstream of the destroyed HindIII site. At the 5' end of
the clone, a SalI site was inserted into the SacI
site located 20 bp downstream of the putative transcription initiation site and 227 bp upstream of the translation initiation codon. The
resulting V1aR sequence, containing a 227 bp 5' untranslated region and the first and second exons separated by a 287 bp
intron, was cloned into the SalI and HindIII
sites of an AAV plasmid derived from pSSV9, a genomic clone of AAV-2
(originally provided by R. J. Samulski, University of North
Carolina, Chapel Hill, NC). The AAV coding sequences of pSSV9
were first excised and replaced with a 0.44 kb simian virus 40 (SV40) DNA fragment (SVpA) containing the SV40 small t intron and
poly(A) signal as well as several unique cloning sites. The viral
iterated terminal repeats required for packaging remained intact in
this plasmid. A PCR-amplified NSE promoter fragment (1 kb in length)
and the pvV1aR sequence were then inserted 5' to the SVpA
segment. Transduction by AAV-2 vectors into the brain is primarily
confined to neurons (Bartlett et al., 1998), but the NSE promoter
further restricts expression to neurons (Peel et al., 1997). The
lacZ vector was prepared in similar manner, incorporating a
PCR-amplified 0.6 kb cytomegalovirus-immediate early
promoter and the 3.7 kb Escherichia coli lacZ
gene sequence. Packaging of all recombinant AAV plasmids was done
according to standard protocols described previously, with some
modifications, by co-complementation with the AAV
trans-acting factors provided on a separate plasmid
and an adenovirus helper (Wu et al., 1998). AAV vector stocks were
titrated by real-time PCR using an Applied Biosystems Prism 7700 Sequence Detection System from Perkin-Elmer Applied Biosystems (Foster
City, CA). Titers of AAV vector preparations as determined by this
technique average 1011/ml.
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Figure 1.
The NSE-pvV1aR plasmid was constructed
by inserting a modified genomic prairie vole V1aR clone
between the NSE promoter (arrow) and the SV40
small t intron and poly(A) signal (pA)
(open box). The V1aR sequence used in the
plasmid spanned from +20 relative to the transcription start site to
the stop codon, with all but 287 bp of the intron deleted. The
striped box indicates V1aR exons.
S, SalI; H,
HindIII; ITR, viral iterated terminal
repeats.
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Behavior testing
Elevated plus maze. The elevated plus maze testing
was performed in an isolated behavior room at 23-24°C. Animals were
brought to the testing room 30 min before testing began to acclimate to the environment. The plus maze apparatus consisted of an open plank
intersecting a walled plank, each measuring 1.4 m in length and
elevated 1 m above the ground. The subject was placed in the center of the apparatus and its location was recorded for 10 min.
Affiliation test. The affiliation test was conducted in a
novel cage between 3:00 and 5:00 P.M. in a quiet room with a
temperature of 23-24°C. After a 30 min acclimation, a 29- to
31-d-old juvenile male prairie vole was placed in the cage and behavior
was recorded for 10 min. Each juvenile was used for no more than two
tests per day.
Partner-preference test. Partner-preference tests were
performed immediately after a 17 hr cohabitation with a nonestrous adult female. The pair were allowed to interact freely but mating did
not occur during the cohabitation period because the females were not
in behavioral estrous. Under these conditions, male prairie voles
typically do not develop a partner preference in <24 hr of
cohabitation unless mating occurs (Insel and Hulihan, 1995; Insel et
al., 1995). The experimental male was placed in the center, neutral
chamber of a three-chambered testing arena in which the partner was
tethered in one chamber and a novel (stranger) female was tethered in a
second chamber. The experimental animal was free to move throughout
these chambers via Plexiglas connecting tubes. During the 3 hr test,
the location and proximity of the male to each female was recorded.
Partner preference was defined as spending more than twice as much time
in the partner's cage relative to the stranger's cage.
Receptor binding analysis
V1aR binding was localized by receptor autoradiography
using a 125I-linear AVP antagonist (NEX
310; DuPont NEN, Boston, MA) as described previously (Young et al.,
1997). Receptor density on autoradiographic film was quantified using
NIH Image software on a Macintosh computer. Bilateral measurements from
three sections per animal were taken, and a mean density measurement
was obtained by subtracting background. Optical densities were
converted to dpm/mg tissue equivalents using
125I microscales (Amersham Pharmacia
Biotech, Arlington Heights, IL) as standards.
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RESULTS |
The animals receiving the NSE-pvV1aR vector into the
ventral pallidal region (V1aR-VP) had nearly a 100%
increase in receptor density in the ventral pallidal area compared with
the control groups (Fig. 2) [ANOVA,
F(2,24) = 6.99, p < 0.004; Fisher's least significant difference (LSD) post hoc
test, p < 0.003 and p < 0.01 compared
with V1aR-CP and lacZ-VP/CP, respectively].
Those animals receiving similar injections into the caudate putamen (V1aR-CP) also had significantly more V1aR binding in the
caudate relative to the V1aR-VP and the lacZ-VP/CP groups
(Fig. 2) (ANOVA, F(2,24) = 22.6, p < 0.001; Fisher's LSD post hoc test,
p < 0.001 compared with each of the other groups).
V1aR binding was not limited exclusively to the ventral pallidal
nucleus in all animals because there was some spread of the virus
beyond the boundaries of this nucleus; however, the ventral pallidum
showed a consistent increase in V1aR binding in all of the
V1aR-VP animals.
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Figure 2.
V1aR binding autoradiograms illustrating
125I-linear AVP antagonist binding in
lacZ-VP/CP males (a, b) and
V1aR-VP males (c, d) at the level of the VP
(arrows). Sections a and
c are slightly rostral to those of b and
d. The V1aR binding field in control animals is most
intense in the more rostral section of the ventral pallidum. V1aR
binding in the caudate putamen of the V1aR-CP males
is illustrated in e. The quantitative analysis (mean ± SEM) of the V1aR binding in the ventral pallidum and caudate
putamen of each group is presented in the bottom right
panel. *p < 0.01.
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Because AVP has been shown to increase anxiety in rats via a
V1aR-dependent mechanism (Landgraf et al., 1995; Liebsch et al., 1996),
the infected voles were first tested on an elevated plus maze to
measure general anxiety. The V1aR-VP group spent
significantly less time on the open arms of the plus maze compared with
the control groups (Fig. 3a)
(ANOVA, F(2,23) = 11.43, p < 0.0001; Fisher's LSD post hoc test,
p < 0.001 compared with each control group). This
suggests that increasing V1aR in the ventral pallidum results in
increased anxiety in this testing paradigm.
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Figure 3.
The effects of V1aR gene transfer on
anxiety, affiliative behavior, and partner-preference formation in male
prairie voles. a, Animals with increased V1aR
expression in the ventral pallidal area (V1aR-VP) spent
significantly less time on the open arms of the elevated plus maze
compared with animals injected with the lacZ control
virus (lacZ-VP/CP) or the pvV1aR vector into
the caudate putamen (V1aR-CP). b,
V1aR-VP males engaged in more affiliative behavior, defined
as either olfactory investigation (filled bar) or
side-by-side contact (open bar), during a 10 min
encounter with an unfamiliar juvenile male. c, After a
17 hr cohabitation with a nonreceptive female, V1aR-VP males
exhibited a partner preference as indicated by spending significantly
more time in side-by-side contact with the partner than with the
stranger in a 3 hr partner-preference test. This pattern was not
observed in either control group. d, Among the
V1aR-VP males, there was a significant correlation between
the duration of social interactions in the affiliation test and the
time spent in side-by-side contact with the partner in the
partner-preference test. *p < 0.05;
**p < 0.005; ***p < 0.0001.
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The V1aR-VP group also displayed elevated levels of
affiliative behavior relative to the control groups. Specifically, when placed in a novel cage and then presented with a novel juvenile male
for a 10 min exposure, V1aR-VP animals spent significantly more time investigating and huddling (side-by-side contact) with the
juvenile compared with the control groups (Fig. 3b) (ANOVA, F(2,27) = 4.85, p < 0.004; Fisher's LSD post hoc test, p < 0.007 and p < 0.04 compared with pvV1a-CP and
lacZ-VP/CP, respectively). Within the V1aR-VP
group, there was no significant correlation between the time spent in
the open arms of the elevated plus maze and affiliative behavior.
To determine whether overexpression of V1aR altered pair-bond
formation, we tested for the development of a partner preference, measured as time spent with the female partner verses a novel female in
a simple 3 hr choice test. The sexually naive males were housed with
nonestrous females for 17 hr during which mating did not occur. The
V1aR-CP and the lacZ-VP/CP males did not
consistently display a partner preference, defined as spending twice as
much time in the cage with the partner than with the novel female. Of
the 17 animals in these groups, 5 exhibited a preference for the
partner, 6 exhibited a preference for the stranger, and 6 did not reach
the criteria for a preference for either animal. In contrast, 12 of the
13 V1aR-VP males exhibited a partner preference. In
addition, as a group, the V1aR-VP animals spent
significantly more time in side-by-side contact with their partner than
with the stranger (Fig. 3c) (p < 0.005, Wilcoxon signed rank test). This was not the case for the
control groups. In the V1aR-VP group, but not in the control
groups, there was a positive correlation between the duration of social
interactions in the affiliation test with the juvenile and the time
spent in contact with the partner in the partner-preference test (Fig.
3d) (r2 = 0.54;
p < 0.004).
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DISCUSSION |
The results from this study also confirm a role for AVP and the
V1aR in the regulation of anxiety, affiliative behavior, and social
attachment. This report is also the first demonstration that complex
social behaviors, such as social attachment, can be facilitated by
viral vector gene transfer. In addition, the results demonstrate that
animals expressing relatively high levels of V1aR in the ventral
pallidum display higher levels of affiliative behavior and are more
likely to form a pair bond than animals with lower levels of receptor
in this region. The results are consistent with the hypothesis that
species differences in V1aR expression may explain species differences
in social organization, particularly because several monogamous species
have higher densities of V1aR in the ventral pallidum than related
nonmonogamous species. These data also imply that individual
differences in the expression of the V1aR gene could account
for individual differences in social behavior and attachment and could
have important implications for psychiatric conditions such as autism.
Dense networks of AVP immunoreactive fibers are found in the lateral
septum and extend ventrally into the ventral pallidal area of the male
prairie vole (Wang et al., 1996). In rats, the septal AVP innervation
arises from the bed nucleus of the stria terminalis and the medial
amygdala (DeVries and Buijs, 1983). It has been demonstrated recently
that AVP infused into the septal area facilitates the formation of
partner preferences in the male prairie vole (Liu et al., 2001).
Together with the present results, these data suggest that
vasopressinergic neurons located in the bed nucleus of the stria
terminalis and the medial amygdala regulate partner-preference
formation through the release of AVP into the lateral septal and
ventral pallidal area, resulting in the activation of ventral pallidal V1aR.
There are two caveats worth noting in our present results. First,
V1aR binding increased in a diffuse region of the medioventral forebrain, sometimes including the portions of diagonal band, ventral
lateral septum, and nucleus accumbens. We have focused on the ventral
pallidum because this region showed increased binding in all of the
experimental animals and because this is the region that expresses the
endogenous V1aR gene in prairie voles. A second issue is the
possibility that regions other than the ventral pallidum are involved
in the AVP-dependent regulation of social behavior and pair bonding.
V1aRs are also found in the amygdala, thalamus, cingulate cortex, and
olfactory bulb. Although our results do not rule out an involvement of
these areas, they do demonstrate that increased levels of V1aR in the
ventral pallidum facilitate partner-preference formation.
The V1aR is a G-protein-coupled, seven transmembrane domain
receptor. Hepatic V1aR is coupled to G q11,
which activates phospholipase C, thereby increasing inositol
triphosphate and intracellular calcium (Wange et al., 1991).
Biochemical studies have suggested that the V1aR is also associated
with other G subunits as well as with
phospholipase A (Strakova et al., 1997). Presumably, the behavioral
effects of V1aR activation in the ventral pallidal area are the result
of the activation of a specific set of second messenger pathways, and
are therefore not necessarily specific for AVP or the V1aR. It would be
interesting to express in the ventral pallidum other G-protein-coupled
receptors that are coupled to the same effector systems in conjunction
with the appropriate ligand administration to determine whether the
behavioral specificity lies in the V1aR itself or in the downstream
second messenger systems.
Microdialysis studies in rats have demonstrated that vasopressin
is released in the brain under certain stressful situations such as
after a social defeat or during a forced swim test (Wotjak et al.,
1996, 1998). Decreasing V1aR expression using antisense oligonucleotides or infusion of a V1aR antagonist decreases anxiety in
rats, as measured by increased time in the open arms of the elevated
plus maze (Landgraf et al., 1995; Liebsch et al., 1996). The present
results are consistent with these observations because animals with
elevated V1aR expression in the ventral pallidum exhibited a decrease
in time spent in the open arms of the elevated plus maze. These same
animals exhibited higher levels of affiliation as measured by increased
time investigating and huddling with a juvenile. It is plausible that
heightened levels of affiliation are attributable to the
increased anxiety. For example, animals that are more anxious may tend
to seek the comfort of social contact. However, the lack of a
correlation between time spent in the open arms of the plus maze and
the duration of affiliative behavior in the V1aR-VP group
suggests that the increases in anxiety and affiliation are probably
regulated by different mechanisms.
The V1aR-VP males exhibited a strong partner preference
after the 17 hr cohabitation without mating. It is important to note that in previous studies from our group, male prairie voles that cohabitated with a female for 24 hr did form partner preferences if
mating occurred, but typically did not if mating did not occur (Insel
and Hulihan, 1995; Insel et al., 1995). Thus, it seems that by
increasing the density of V1aR in the ventral pallidum, the amount of
social stimulation required to form a partner preference was decreased.
Also, the probability of forming a pair bond during this short exposure
period could have been affected by increased affiliative behavior
displayed by the males. Among the V1aR-VP males, there was a
correlation between the duration of affiliative behavior with the
juvenile and the time spent in contact with the partner. Perhaps the
increased social interest expressed in these animals resulted in
increased social stimulation, thereby facilitating the formation of the
pair bond.
This is the first study to implicate the ventral pallidum in the
regulation of social behavior and attachment. It should be noted that
the field of V1aR binding in the prairie vole ventral forebrain is not
restricted to the ventral pallidum but likely extends into the ventral
lateral septum and substantia innominata. Thus we cannot rule out a
role for these structures in the regulation of AVP-dependent behaviors.
However, functional anatomical studies of the ventral pallidum make it
a particularly interesting candidate site for a role in pair-bond
formation. The ventral pallidum is a major relay of the shell of the
nucleus accumbens and, like the nucleus accumbens, receives
dopaminergic input from the ventral tegmental area (Klitenick et al.,
1992). This striatopallidal system is an important neurobiological
substrate for the rewarding and reinforcing properties of natural
stimuli and psychostimulants (McBride et al., 1999). Infusion of
psychostimulants directly into the ventral pallidum leads to the
development a conditioned place preference for the environment in which
the injections were experienced (Gong et al., 1996). Given the
abundance of V1aR in the prairie vole ventral pallidum and its role in
conditioned place preference, we hypothesize that AVP released during
social interactions or mating activates V1aR in the ventral pallidum. Activation of this reward circuitry then reinforces this
behavior, leading to an increase in social interactions. In a mating
pair, the reinforcement is powerful enough to lead to a conditioned partner preference in the monogamous prairie vole and thereby initiates
the formation of a pair bond. The lack of V1aR in the ventral pallidum
of nonmonogamous vole species may explain their inability to form
partner preferences after mating. There are most certainly other
genetic, neurochemical, or anatomical differences between monogamous
and nonmonogamous species that contribute to their diverse social
behavior; however, the viral vector approach provides an opportunity to
test this hypothesis. It should be possible to elevate V1aR expression
in the ventral forebrain of nonmonogamous montane or meadow voles and
determine whether partner preferences are formed.
The role of AVP in facilitating pair bonding in the male prairie vole
is remarkably parallel to that of oxytocin in the female prairie vole.
In the female it is oxytocin, not vasopressin, that facilitates the
formation of the pair bond with the mate (Insel and Hulihan, 1995).
Oxytocin antagonist infused into the nucleus accumbens prevents
partner-preference formation in the female (Young et al., 2001). In
addition, prairie voles have much higher concentrations of oxytocin
receptors in the nucleus accumbens than do nonmonogamous vole species
(Insel and Shapiro, 1992). Dopamine D2 receptor antagonists infused
into the nucleus accumbens also prevent partner-preference formation
(Gingrich et al., 2000). Thus it appears that pair bonding is
facilitated in a sex-specific manner, by two different neuropeptide
systems acting at two separate points in a common neural circuit.
Our results are consistent with the hypothesis that the striatopallidal
reward circuitry facilitates certain aspects of affiliation and social
attachment, implying common neural pathways for social attachment and
the reinforcing effects of drugs of abuse (Panksepp, 1998). A recent
functional magnetic resonance imaging study examined the pattern
of brain activation and deactivation in human subjects as they viewed
photographs of individuals with whom they reported to be romantically
in love. The regions of activation were strikingly similar to those
activated in studies of cocaine- and µ opioid agonist-induced
euphoria (Bartels and Zeki, 2000). Although the role of vasopressin in
human social attachment is unclear and the distribution of V1aR in the
human brain has not been fully described, it is intriguing to consider
that plasma vasopressin levels are elevated during sexual arousal in
the human male (Murphy et al., 1987). Although increases in plasma AVP
released from the posterior pituitary do not necessarily correspond to
releases in the brain, these findings raise the possibility that
similar neural mechanisms may underlie pair-bond formation in rodents and human males.
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FOOTNOTES |
Received May 16, 2001; revised July 6, 2001; accepted July 6, 2001.
This work was supported by National Institute of Mental Health Grants
58824 and 56897 (L.J.Y.) and by National Science Foundation Grant IBN
9876754 (T.R.I.).
Correspondence should be addressed to Larry J. Young, Center for
Behavioral Neuroscience, 954 Gatewood Drive, Emory University, Atlanta,
GA 30322. E-mail: lyoun03{at}emory.edu.
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