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High on Fidelity

Marla V. Broadfoot

Monogamy is extremely rare. Of the 4,000 or so mammalian species, only a few percent are monogamous. What makes this tiny minority stay attached to one mate? Investigators are coming closer to answering this question by studying voles, small rodents commonly known as field mice.

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Although the various vole species look pretty much the same on the outside, their inner drives can be quite different. Prairie voles (Microtus ochrogaster) are highly social and monogamous, whereas the closely related montane voles (M. montanus) are solitary and promiscuous. Monogamy is defined in the laboratory as the formation of a pair-bond, where the vole under study chooses to associate with a steady partner over a novel mate. Two similar hormones that influence neural activity appear to play a critical role in the formation of this pair-bond: vasopressin, which affects male reproductive and social behaviors (such as communication, aggression and sexuality) and its sister peptide oxytocin, which is involved in promoting maternal nurturing and sexual receptivity.

Almost a decade ago, Thomas Insel, Director of the Center for Behavioral Neuroscience at Emory University, and colleagues at the National Institute of Mental Health and the University of Maryland implicated vasopressin and oxytocin in controlling the preference for particular partners in both male and female prairie voles. These investigators found that giving a male vasopressin causes it to stay with its mate, whereas blocking this hormone prevents a pair-bond from forming. The scientists saw similar effects in female prairie voles, with oxytocin determining the extent of pair-bonding. In contrast, the administration of these substances had no influence on social interactions in the promiscuous montane voles. Surprisingly, vasopressin and oxytocin are naturally found at similar levels in both prairie and montane voles.

Although the same molecular receptors bind these hormones in both monogamous and promiscuous voles, these specialized structures are dispersed differently in the brains of each species. The dissimilarity in receptor distribution has an enormous effect on social behavior and attachments. In monogamous voles these receptors are found in so-called reward regions of the brain where addictive drugs act. "When a monogamous vole mates, it is as if it got a hit of cocaine. The vole becomes addicted to whomever he was mating with," says Insel.

Larry Young, a collaborator of Insel's in the Department of Psychiatry and Behavioral Sciences at Emory University, chose to examine the connection between high levels of vasopressin receptors in this area and monogamy. Specifically, he incorporated the gene for the vasopressin receptor into a virus, which was then injected into a reward region, selectively increasing the concentration of vasopressin receptors there. He, Insel and other colleagues from Emory University and the Harvard Institutes of Medicine reported their findings in the September 15, 2001 issue of The Journal of Neuroscience.

Voles infected with the virus carrying the gene for the vasopressin receptor were more social and were able to pair bond even without mating. "Now it is love at first sight," says Young. "Normally," he explains, "they have to mate all night long for the pair-bond to form. By increasing the receptors, we were able to reduce the threshold of social stimuli needed to form that bond." Young and Insel are now manipulating the amount of oxytocin receptors in the brain of female prairie voles. These investigators expect that the females will respond in the same way as the males, forming a preference for one partner without the need for sex.

Israel Lederhendler, chief of the Behavioral and Systems Neuroscience Program at the National Institute of Mental Health, believes that this research demonstrates that genetic tools can be employed to understand the mechanisms of complex social behaviors. And Lederhendler expects this approach will eventually yield big payoffs: "We are only beginning to scratch the surface."

Insel and Young's work highlights the fact that certain behaviors don't require much cognitive input. If the tendency to be monogamous is determined by the distribution of vasopressin receptors in voles, one wonders what could be accomplished in humans. Could Young's virus be used to turn a Hugh Heffner into Mr. Mom? Nobody knows. It's been established that vasopressin is released into the bloodstream during sexual arousal in men—but whether that corresponds with higher uptake in the brain is unclear. Although receptors for both vasopressin and oxytocin are found in the human brain, the distribution does not resemble that seen in either the monogamous prairie vole or the promiscuous montane vole. So Young is skeptical that an engineered virus could ever be used to make people fall—and stay—in love. "I do not foresee that we are ever going to try to control human behavior with fidelity drugs."

Young suggests that his work might, however, shed light on the biological basis of our inherent sociality. And a greater understanding of those tendencies might lead to treatments for mental and behavioral disorders that interfere with the capacity to form social bonds. Autism, for example, appears to be a genetic disorder that disrupts a person's ability or inclination to connect with others, and the same genes that control monogamy in voles could conceivably be involved.—Marla Vacek

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