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Gene transfer enhances pair bonding in monogamous voles

Emory University Health Sciences Center

Scientists at Emory University 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. 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. The research is reported in the September 15 issue of the Journal of Neuroscience.

Emory University neurobiologist Larry J. Young, Ph.D., of the Center for Behavioral Neuroscience and the Yerkes Primate Research Center, 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 pallidum -- an 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 Dr. Young, the research group included Lauren J. Pitkow, Ph.D., Catherine A. Sharer, Ph.D. and Thomas R. Insel, M.D. of the Center for Behavioral Neuroscience and Xianglin Ren, Ph.D. and Ernest F. Terwilliger, Ph.D., 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 two- to five- months old and were 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% 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 ten 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 out of 13 of the experimental voles spent more than twice as much time in the partner's cage than in the stranger's cage, whereas there was no particular preference for the partner 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.

Scientists previously have demonstrated that monogamy in voles, including the formation of pair bonds, is enhanced by vasopressin and that an antagonist for the vasopressin receptor can prevent the formation of pair bonding. Scientists also know that the distribution of the vasopressin receptor within certain regions of the brain is dramatically different between monogamous and non-monogamous species of voles. All monogamous vole species, even though they may be unrelated, have denser vasopressin receptor binding in the ventral pallidal region of the brain than do non-monogamous vole species.

"We also know that the ventral pallidum region is involved in reinforcement and addiction," said Dr. Young, "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 in humans of psychiatric diseases.

"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," Dr. Young points out. "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."


The research was supported by the National Institute of Mental Health and the National Science Foundation.

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