Mice can thank a hormone for the memories

What’s the difference between a normal mouse and a socially forgetful one, the latter a furry analogue of the party guest who asks someone’s name for the fourth time?

The difference could be a small neuropeptide, say researchers in the July Nature Genetics.

Oxytocin, a hormone with a history of controversy (SN: 10/19/96, p. 246), may facilitate social recognition in mice but not other types of memory, the team concludes. Besides demonstrating two distinct mouse-memory systems, the finding bolsters evidence that oxytocin plays an important role in mammal behavior.

The researchers, led by James T. Winslow of the Yerkes Regional Primate Research Center at Emory University in Atlanta, compared the performance of normal mice with that of mice lacking the gene for oxytocin. In social situations, normal mice quickly get used to a strange mouse: Up to an hour after their first meeting, the mice forgo the extensive sniffing that accompanied their initial encounter.

Not so for the modified, or oxytocin-knockout, mice. They sniffed as much during subsequent meetings as on a first encounter. This effect disappeared when researchers injected oxytocin directly into the brains of the genetically deficient mice.

Reacting to nonsocial stimuli, however, normal and knockout mice were comparable. Both groups remembered the scent of chocolate and lemon, and both used spatial memory equally well in navigating two kinds of mazes.

How likely is it that oxytocin plays a similar role in humans, helping us recall if not madeleines, at least, perhaps, Madeleine?

It’s difficult to make a direct link, says Winslow. In mice, pheromones influence social recognition. They’re processed by a sensory sac called the vomeronasal organ. Although people possess a rudimentary vomeronasal organ, its contribution to our social behavior isn’t clear.

For a decade, researchers have suspected oxytocin to be crucial for sexual and maternal behavior in mammals, but its role has defied straightforward interpretation. “I see no evidence to contradict the notion that oxytocin is very important to mammalian sociality,” says C. Sue Carter, a zoologist at the University of Maryland, College Park. She adds, however, that the hormone’s exact functions vary widely by species.

For example, prairie voles treated with oxytocin double their social contact, Carter says. In rats, oxytocin usually has more carnal effects. In mice, Winslow’s team says, the hormone can help or hinder social memory, depending on dose.

The oxytocin rap sheet is even more diverse in people. The hormone’s concentrations fluctuate in the blood of both men and women, peaking at orgasm. No one knows why. Some studies have suggested that oxytocin mediates positive emotions in intimate relationships (SN: 8/7/99, p. 90). Doctors routinely give oxytocin to induce labor, and increased blood concentrations caused by heat and humidity may cause premature labor (SN: 5/20/95, p. 315).

Some of the excitement over the hormone ebbed in 1996 when researchers produced oxytocin-knockout mice. The creatures vexed the scientific community by showing normal maternal behavior, albeit without lactation (SN: 10/19/96, p. 246).

The strain that produced the original knockout mouse had unusually strong maternal behavior, Winslow explains. This confounded the results, he says. It also highlights the problems of working with genetically altered animals, which may differ from their normal counterparts in unanticipated ways, he adds.

The new study avoids the difficulty of the original experiment, Winslow claims, because the normal and modified mice behaved similarly in nonsocial tasks.

Keith Kendrick, a neurobiologist at the University of Cambridge in England, praises the study. He cautions, however, that “it is still comparatively premature to conclude that [oxytocin’s] release in the brain selectively enhances formation of such social memories.” The mere fact that mice were isolated in order to test their memory, he notes, “itself promotes changes in the brain that might have interacted with the lack of an oxytocin gene to produce behavioral effects.”

Winslow agrees that future studies need to find where in the brain oxytocin acts to affect social memory. He maintains, however, that the team’s work shows that “oxytocin appears to be important in some ways in normal development of social behavior in several species.” He adds that the hormone “looks like a pretty good candidate, I think, for a possible role in the normal social development of humans, as well.”