October 8, 2001
Young: Gene transfer strengthens vole pair bonds
By Holly Korschun
Yerkes scientists have been able to increase bonding behavior in monogamous
male prairie voles by transferring a receptor gene for the neuropeptide
arginine vasopressin (AVP) into a particular region of the brain, according
a study published in the Sept. 15 Journal of Neuroscience.
The study reinforces previous findings that monogamy in voles, including
the formation of pair bonds, is enhanced by vasopressin, and it is the
first study to demonstrate that complex social behaviors, such as social
attachment, can be increased by viral vector gene transfer.
Neurobiologist Larry Young of Yerkes Center for Behavioral Neuroscience
(CBN) and his colleagues used an adenovirus vector to deliver the gene
for the vasopressin receptor (V1aR) into an area of the voles brains
called the ventral palliduman area already known to naturally express
V1aR in monogamous voles.
Vasopressin is a neurotransmitter responsible for sending certain signals
within the brain. The gene transfer caused the voles to overexpress V1aR,
thereby increasing the density of vasopressin binding to the receptor.
In addition to Young, the research group included CBN scientists Lauren
Pitkow, Catherine Sharer and Thomas Insel, and Xianglin Ren and Ernest
Terwilliger of the Harvard Institutes of Medicine.
The scientists used three groups of male prairie voles in their experiment.
Although voles vary widely in their bonding tendencies, prairie voles
are known to form strong pair bonds. All the voles were 25 months
old and sexually naive.
The experimental group received infusions of V1aR into the ventral pallidal
region of the brain. One control group received the same injection into
a region of the brain that does not naturally express V1aR, and the other
control group received a control vector instead of V1aR.
The scientists tested each group for the presence of the vasopressin
receptor and found that the experimental group had nearly a 100 percent
increase in receptor density in the ventral pallidal area compared with
the control groups.
Because vasopressin has been shown to increase anxiety in rats, the scientists
also tested the voles in a maze that measures general anxiety and found
that the experimental group exhibited more general anxiety than the control
groups. When they placed the voles in cages with other juvenile males
for 10 minutes, the experimental group spent much more time huddling and
investigating the other animals than did the control groups.
In a partner preference test, the male voles were first allowed to interact for 17 hours with a nonestrous adult female, but the voles did not mate. Following the cohabitation, the experimental males were individually placed in chambers between their partner and another unknown female.
During a three-hour test, 12 of the 13 experimental voles spent more
than twice as much time in the partners cage than in the strangers
cage, while there was no partner preference in the control animals. In
past experiments, male prairie voles have not developed a partner preference
in less then 24 hours of cohabitation unless mating occurs.
The study is the first to identify the ventral pallidum region of the
brain as a key to social behavior and attachment. In addition, it shows
that animals expressing higher levels of the vasopressin receptor in the
ventral pallidum display higher levels of affiliative behavior and are
more likely to form a pair bond than animals with a lower level of receptor
in that brain region.
We also know that the ventral pallidum region is involved in reinforcement
and addiction, Young said. Thus we hypothesized that vasopressin
receptor activation in this region promotes pair-bonding through a mechanism
similar to conditioning. When vasopressin is released during social interactions
or mating, it activates the V1aR receptor in the ventral pallidum, setting
up a reward circuit that reinforces this behavior, thus leading to increased
social interactions and a conditioned partner preference in monogamous
prairie voles. Non-monogamous voles lack v1aR in their ventral pallidums,
which may explain their inability to form partner preferences.
The scientists believe their research may be helpful in developing future
studies of psychiatric diseases in humans.
Although we know that social bonding and affiliation are essential components of human society, we know very little about the brain circuitry that regulates this behavior, Young said. When these circuits are disrupted, it may result in psychiatric diseases such as autism that are characterized by social problems. Voles provide a useful model for studying the molecular mechanisms underlying species differences in social organization.