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Worried to Death: Lifelong inhibitions hasten rodents' deaths

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11:33am, December 10, 2003
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Some animals shy away from novel settings all their lives, preferring the predictability of familiar surroundings. Although this can be a safe strategy in the short run, it may have a fatal drawback down the line.

A new study finds that novelty-averse laboratory rats, after reaching maturity, died at markedly younger ages than did their more adventurous comrades. Heightened hormone responses to mildly stressful events throughout life ultimately undermined the capacity of the inhibited rats to resist tumors and other health threats, contend Sonia A. Cavigelli and Martha K. McClintock, both psychologists at the University of Chicago.

In essence, stress responses cause the inhibited rats to age prematurely, the researchers conclude in the Dec. 23 Proceedings of the National Academy of Sciences. These animals exhibit a 20 percent reduction in maximum life span compared with that of their bolder brethren.

"This is the first study to show that a psychological trait present from infancy can have life span consequences," McClintock says. "I suspect this finding applies to people as well as to rats."

An initial experiment with male rats confirmed that the tendency of animals either to avoid or explore new environments persisted into adulthood. Twelve animals that, when placed in an unfamiliar chamber at age 4 months, avoided contact with items there, were equally cautious 4 months later. Likewise, 16 rats that readily touched and climbed on objects in a novel setting at 4 months retained their curiosity.

Blood tests revealed comparable baseline concentrations of the stress hormone corticosterone in cautious and bold rats. However, after being placed in and 5 minutes later removed from a novel setting, the reserved animals displayed elevated corticosterone concentrations for at least 40 minutes, while the bolder group's corticosterone readings rose transiently before dipping back to baseline.

In another experiment, the scientists studied 14 pairs of brothers. In each pair, tested at around 20 days of age, one rat exhibited a fear of novelty and the other a willingness to explore. These traits remained stable through adulthood.

When briefly restrained in a tube at age 15 months, inhibited rats mounted a much larger corticosterone response than the bold rats did. This disparity lasted for at least 2.5 hours after removal from the tube.

The novelty-averse rats commonly lived about 600 days, compared with 700-day lifetimes for the bolder rats. The strain of rats used in the study are genetically predisposed to developing pituitary gland tumors, and many of the deaths were due to this condition. However, the reserved rats died more often than their bolder brothers did from relatively small tumors.

An inhibited lifestyle comes with a health trade-off, McClintock theorizes. Cautious rats avoid predators and other dangers in their prime, but accumulated exposure to high levels of stress hormones renders them vulnerable to disease later in life.

"These are potentially important findings, but I'm cautious about accepting them," remarks psychologist Jerome Kagan of Harvard University, who studies inhibited children. The results need to be confirmed in other strains of rats and with different measures of inhibition, he says.

Moreover, Kagan notes, risky behavior, rather than inhibition, causes people to die young.

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