Macho Mouse No More

What makes some males form lasting relationships, while others are promiscuous and irresponsible? The answer may lie, at least in part, in the way the brain responds to a hormone known as vasopressin, according to a study in today's issue of Nature. The dramatic proof came in an experiment in which the researchers were able to make a mouse more caring for females by giving it the vasopressin receptor gene from the prairie vole, well known for being faithful and social.

Previous research had suggested that vasopressin plays a role in social behavior, ranging from aggression and territorialism to pair bonding and caring for young. To study the hormone's mechanism of action, neuroendocrinologist Larry Young and colleagues at Emory University in Atlanta turned to two rodent species that look identical but have strikingly different behavior patterns: the prairie vole, which is monogamous, tends and defends its nest, and seeks out the company of other voles; and the mountain vole, which shuns other voles' presence and is promiscuous.

The two species' genes for the vasopressin receptor--which relays the hormone's message to brain cells--have slightly different "promoters," the switches that turn genes on and off. As a result, the receptors are concentrated in different parts of each species' limbic system, the part of the brain that controls drive and emotions. To see if differences in response to vasopressin accounted for the contrast in personality, the researchers took males from each species and paired them with females, which had been neutered to prevent them from leading on the males. They then injected the males with vasopressin. The prairie voles responded with increased displays of chivalry, included sniffing, licking, and grooming the females, but the mountain voles remained aloof as ever.

Next, the scientists cloned the gene from the prairie vole's vasopressin receptor and implanted it in an embryo of the less sociable laboratory mouse. (Making a transgenic mountain vole would have been much more difficult.) The resulting mice had the prairie voles' receptor distribution in their limbic systems; and although not monogamous, they were more devoted than normal mice to female cagemates, showing some of the other vole's eagerness in sniffing and grooming. "This is the first time anyone's used a single gene to implant something as complex as a behavioral trait into another species," says Young.

"It's a brilliant piece of work," says Dean Hamer, a behavioral geneticist at the National Cancer Institute. "It confirms a theory that's been kicking around for some time: What really makes species different isn't individual chemicals but where they work and how they're controlled." Little is known about the effects of vasopressin in human males, but, says Hamer, "there's every reason to think the same principle will apply--although one gene probably won't turn a Bill Clinton into a model of fidelity."