AGGRESSION RESEARCH: OF MICE AND (MAYBE) MEN

A new wave of violence is being reported in France and the United States -- but this wave involves laboratory mice, not people. Scientists in both countries have recently discovered that abnormalities in brain chemicals can turn normal mice into violent, sexually predatory animals.

The previous issue of Crime Times, Vol. 1, No. 3, Page 1 reported on findings by Olivier Cases et al. of France, who discovered that mice lacking in monoamine oxidase A (MAOA) were very aggressive as adults, and that their mating behavior was much rougher than that of normal mice.

Now a U.S. study suggests that the lack of another brain chemical -- nitric oxide -- can also create aggressive "rapist rodents." And a new French study indicates that mice lacking one type of serotonin receptor in their brains are much more violent than their normal counterparts.

When researchers at Johns Hopkins University genetically engineered mice in order to study strokes, the results were unexpected. "Upon routine morning examinations," Randy Nelson and colleagues note, "[we] often discovered one or two dead mice in each cage." The mice weren't dying of natural causes, but were being killed by other members of the mouse colony.

The mice committing these savage murders lacked a gene essential for the production of the neurotransmitter nitric oxide. Further investigation revealed that the knockout mice (those lacking the gene) originated three to four times as many aggressive encounters as other mice, and exhibited only one-tenth as much submissive behavior. Unusual behaviors were not seen in female knockout mice.

Nelson et al. also report that male knockout mice were highly aggressive when mating, "display[ing] excessive and inappropriate mounting behavior associated with substantial vocal protestations by the females."

The researchers note that testosterone levels were normal in the knockout mice, and that their behaviors were not related to any abnormalities in sense of smell, strength, agility, or fear levels. They also point out that the mice showed no neuroanatomical or physiological disturbances, meaning that "it is highly probable that the behavioral abnormalities we have observed are direct, selective consequences of the loss of nNOS [the enzyme necessary for formation of nitric oxide] and not secondary to global physiological disruptions."

The researchers say that "though direct comparisons are not feasible, the sexual and aggressive aberrations of [mice lacking the nNOS gene] seem more pronounced than those reported with deletion of other genes. Accordingly, nitric oxide may be a major mediator of sexual and aggressive behaviors, relevant for studies of their biological determination in humans as well as mice."

In France, Frederic Saudou et al. engineered a different type of mice: their experimental animals' brains lacked one type of receptor for the chemical serotonin.

Low levels of serotonin, a neurotransmitter, have been linked to impulsive violence, suicide, alcoholism, and depression (see Crime Times, Vol. 1, No. 1/2, Page 7). There are at least 14 types of serotonin receptors, and Saudou and colleagues created their mutant mice as part of their investigation into the roles each type of receptor plays in behavior.

The French researchers found that mice missing the 5-HT-1B receptor "attacked [normal mouse intruders] faster and more intensely than did wild-type mice, suggesting the participation of 5-HT-1B receptors in aggressive behavior." Their findings, they say, indicate that 5-HT-1B receptors may be activated in response to stressful situations. "When the mutants are housed as a group," the researchers say, "they are not more aggressive than [other] mice. However, after a month of isolation and in the presence of an intruder, the mutants are significantly more aggressive than the [other] mice."

"Behavioural abnormalities in male mice lacking neuronal nitric oxide synthase," Randy Nelson, Gregory Demas, Paul Huang, Mark Fishman, Valina Dawson, Ted Dawson, and Solomon Snyder, Nature, Vol. 378, Nov. 23, 1995. Address: Solomon Snyder, Psychiatry and Behav. Sci., Johns Hopkins University, 725 N. Wolfe St., Baltimore, MD 21205.

"Enhanced aggressive behavior in mice lacking 5-HT-1B receptor," Frederic Saudou, Djamel Ait Amara, Andree Dierich, Marianne LeMeur, Sylvie Ramboz, Louis Segu, Marie-Christine Buhot, and Rene Hen, Science, Vol. 265, Sept. 23, 1994. Address: F. Saudou, Laboratoire de Genetique Moleculaire des Eucaryotes du CNRS, U184 de L'INSERM, Faculte de Medecine, 11 rue Humann, 67085 Strasbourg Cedex, France.

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