Could there be a biological basis for love? Cort Pederson says yes. His studies of the hormone that turns on maternal behavior have led him to postulate that we have one biological system to form emotional attachments and one to maintain them. And Josephine Johns has found that cocaine interferes with the first one.

We think of love and human relationships as emotional, spiritual, and perhaps mystical. But could there be a biological explanation for the bonds between people, even between mother and child?

Cort Pedersen, professor of psychiatry, thinks so. His studies of the maternal behavior of rats have led him to believe that there is one biological system to initiate emotional attachments and another to maintain them.

Pederson’s work began in the 1970s, when researchers suspected that a hormone called “oxytocin” played a role in maternal behavior. They recognized that large amounts of oxytocin are released into the bloodstream before delivery—just when the female rat becomes interested in her pups.

There had been a number of experiments to see if oxytocin released into the blood affected maternal behavior,” Pedersen says. “All had turned out negative, but that was before people realized oxytocin was also in the brain.”

Pedersen and his colleagues blocked oxytocin in the brains of mother rats, and the mothers immediately lost interest in their pups. They spent less time nursing, took longer to begin nursing, and did not always retrieve stray pups. The inverse was also true: Virgin rats who had been given both oxytocin and estrogen—which increases the brain’s receptivity to oxytocin—began to act like mothers. The effect took less than 40 minutes.

Later work by Pedersen’s group showed that, near the end of pregnancy, oxytocin levels change dramatically in areas of the brain involved in mothering behavior—more evidence linking the hormone to maternal instincts.

To explore oxytocin’s role further, Pedersen’s group studied mother rats that had five-day-old pups. Some mothers remained with their pups (the control group), some were separated from their pups for nearly a week, and some lived in “proximal separation,” with the pups in a cage next doorwhere the mother could see, hear, and smell her young but couldn’t nurse them.

We wanted to see how quickly the females would resume maternal behavior once we returned the pups,” Pedersen said. “After four to six days, we gave the mothers access to the pups. Bang! The proximally separated group started mothering right away.”

The researchers assumed that a release of oxytocin caused the rapid resurgence of mothering behavior. They repeated the experiment but blocked oxytocin in the mothers before returning the pups. This time, the proximally separated mothers didn’t resume their caretaking, though the same treatment had no effect on the control group. It seemed that the mothers who experienced proximal separation needed the hormone to become mothers again.

Pedersen thinks physical contact with the pups, particularly suckling, mobilizes a “maintenance” system which doesn’t depend on oxytocin. Other observations support the idea. Oxytocin levels in the mother’s brain return to normal several days after delivery, and blocking the hormone at that time doesn’t diminish the mother’s responsiveness to her pups.

It seems as if the brain is wired so that the oxytocin system initiates maternal drive,” Pedersen says. “But, once there is consummation of maternal behavior through significant physical contact, another system takes over.”

Three days of proximal separation are needed to revert to the oxytocin-dependent system. And having no contact with pups seems to shut down both mechanisms: After being completely separated from their pups for four days, mothers hardly bothered to retrieve youngsters who left the nest.

The whole purpose of maternal behavior is to make sure the pups are fed and kept warm,” Pedersen says. “Stimulation from suckling tells the mother that the infants are being fed. Then the initiation system isn’t needed, and the maintenance system takes over.”

In addition to providing specific information about maternal behavior, Pedersen thinks this research will help us under stand the nature of human relationships and loss.

Initially, as we’re falling in love, passions are very strong, but they seem to fade over time,” Pedersen says. “It may be that we’re experiencing a shift from the initiation to the maintenance mechanism.

If there’s a breakup or loss, the maintenance mechanism dissolves, ” Pedersen says. “But we have very vivid memories, and we experience situations—places or friendsthat remind us of the other person. This is proximal separation: You can’t ‘consummate’ the relationship, but you are still exposed to stimuli from the other person. That may reactivate the mechanisms that initiated the relationship.”

Maybe Pedersen has figured out why, long after a break-up, hearing a particular song can make us miss someone. The body is waiting for love.

The Broken Bond

Cocaine-addicted mothers say they love their children but often neglect or mistreat them,” says Josephine Johns, research associate professor of psychiatry and adjunct professor of psychology. “I began to question if cocaine prevents the women from bonding normally with their children.”

Johns suspected that cocaine might interfere with oxytocin, the hormone that initiates maternal behavior in rats. She suggested it to Pedersen and other colleagues, and their early work led to a five-year grant from the National Institutes on Drug Abuse. After only one year, Johns and her students—with the help of Pedersen and of George Mason and Linda Noonan, research professors in psychiatry—have unexpected results.

The researchers compared normal mother rats to a chronically treated group, which received cocaine until the day before they delivered their pups, and to an acutely treated group, which received a single dose after delivery. In all cases, the pups were removed from the cages after delivery and replaced with surrogates that had no prenatal exposure to cocaine.

Both the chronic and acute mothers showed less interest in their pups than the control group did. The cocaine-treated mothers delayed nursing, spent less time at it, and took longer to retrieve wandering pups. Some chronically treated mothers didn’t build nests.

This neglect mimicked the behavior of some human “crack-cocaine moms,” and it looked familiar to Pedersen. The cocaine-treated rats behaved like rats who, shortly after delivering, were given substances to block oxytocin. However, an important difference was a dramatically elevated level of aggression in the chronically treated animals.

Normally, a mother rat will defend her pups against an intruder, particularly a male. But the chronically treated mothers were so aggressive toward intruders that some experiments had to be stopped because the intruder’s life was threatened. During these frenzied attacks, the mothers disregarded the pups, running them over and endangering them. Johns suggests that these rats may be misinterpreting cues from the intruder as threatening.

Surprisingly, Johns and her students found that the acutely treated rats were less aggressive than normal ones. Mothers treated with larger doses of cocaine were more likely to allow an intruder to attack their pups.

The researchers found a link between oxytocin and the amygdala, an area of the brain associated with rage and other emotional behavior. Chronically treated mothers had significantly reduced levels of oxytocin in the amygdala when they were most aggressive, while acutely treated mothers had normal or nearly normal levels. These results suggest that oxytocin plays a role in regulating maternal aggression through specific brain areas.

With cocaine’s disruption of the initiation of maternal behavior firmly established, Johns is wondering how the drug affects mother-infant interactions further down the road. And she wants to find out if treating a mother with oxytocin will ameliorate some of cocaine’s effects, perhaps enhancing the mother-child bond.