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September 15, 1999
EMBARGOED FOR RELEASE ON
WEDNESDAY, SEPT. 15, 1999
Brain Chemical Mellows Male Mice,
A chemical messenger in the brain that dramatically decreases
aggressive behavior in male mice appears, on the contrary, to be
essential to a mother mouse's ability to lash out at strange mice
in defense of her pups, according to a new report by scientists
at The Johns Hopkins University.
Makes Mouse Mothers Tough
The new results, reported in the September 15 issue of the
Journal of Neuroscience, establish a potential link
between a single brain chemical the neurotransmitter nitric
oxide and opposing effects in male versus female brains.
"This result was a big surprise, given what we saw in the male
mice," says Stephen Gammie, a postdoctoral fellow in the
Department of Psychology at
Johns Hopkins and lead author of the paper. "This may reflect the
fact that male and female rodents need to be aggressive in
different situations, and as a result have different mechanisms
for controlling aggression. It's one more piece of evidence of
how complex brain chemistry is, even at the level of the
The new findings could also help scientists begin to understand
at a very basic level some of the brain and behavioral changes
brought about by pregnancy.
The experimental mice, originally created by scientists to study
brain damage from stroke, have been given a defective copy of the
gene for nitric oxide synthase, a protein that creates nitric
oxide for use as a signal in brain cells. Theoretically, this
produces a near-complete absence of nitric oxide in brain
ago, researchers at Johns Hopkins announced that this
modified mouse line had suffered an unexpected side effect: the
males were unusually aggressive, relentlessly attacking other
males and ignoring female rejection of attempts to mate. The
latest research sought to expand that finding by determining the
effect of a lack of nitric oxide on females' aggressiveness.
"Male mice are aggressive in a variety of contexts, but the
female mouse normally only attacks other mice when she's caring
for pups after a pregnancy and is approached by a strange male
professor of psychology and neuroscience and a co-author of the
new paper. "The female's aggression reduces the danger that the
male will attack her pups."
For the experiment, funded by a grant from the National
Institutes for Mental Health, researchers used nine genetically
modified pregnant mice and 13 normal pregnant mice. Four days
after the mouse pups were born, they began to expose the new
mothers to strange male mice for ten minutes daily. To protect
them from harm, the pups were removed from the cage before each
exposure, a step previously shown to have no effect on maternal
aggression. The results were videotaped.
The experimental mice made significantly fewer efforts to drive
off the stranger, and often failed to make any discernible
"Compared to the normal mice, the experimental mice spent
one-fifteenth of the time attacking the strange males," says
Gammie. "On the rare occasions when the experimental mice did
appear to make some kind of attack, it was so mild that it
produced little reaction in the male mice." When exposed to the
attacks and bites of normal females, males either fought back or
To see if the genetic alteration had affected other aspects of
maternal behavior, Gammie and Nelson gave mice from both groups a
"pup retrieval" test immediately after exposures to the male
mice. They returned the pups to the cage at random spots, and
noted the time it took the mothers to gather the first and fourth
pups back to their nests.
"There were no significant differences in this and other aspects
of maternal behavior," Gammie says. "The experimental mice seemed
perfectly good at nest-building, and the weight and survival rate
among their pups was actually higher."
Researchers also analyzed the brains of the mice for citrulline,
a chemical byproduct created when brain cells make nitric oxide.
The number of brain cells making the compound significantly
correlated with the aggressiveness of the female mouse. In
instances where males were aggressive, though, no significant
citrulline production occurred.
"In males, it's useful to be aggressive throughout the breeding
season because this can increase access to females and also can
lead to attacks on the pups of another male," says Gammie,
speculating on the reasons for the differences in brain
chemistry. "For females, it is dangerous to challenge a larger
male, so it makes sense to limit expression of aggression to
times when the pups are in the nest and need protection. Females,
then, need a way of quickly turning on aggression, but then
quickly turning it off."
To further explore the link, scientists plan to test whether they
can replicate the effects of the altered gene using nitric-oxide
suppressing drugs. Scientists hope the new experiment will
solidify the connection between nitric oxide and maternal
aggression, and help them more closely understand how brain
changes create aggression.
Because of continued scientific interest in the behavior of these
mice, they will not be made available for filming. Many of the
behavioral observations of mice in this study were videotaped,
and a tape of highlights from these observations has been
produced for your use. Contact
Michael Purdy at the phone
number or addresses above.
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