Pugnacious mice lack serotonin receptor.

Disturbances in serotonin's complex web of action have been blamed for many disorders, including migranes, depression, and schizophrenia. As researchers discover more types of receptor molecules for his neurotransmitter--14 are currently known--scientists are gaining greater insights into how a single transmitter can be involved in myraid functions.

Now, researchers say they have new evidence that serotonin's action on one of these receptors, called 5HT1b, helps dampen aggression. The absence of that receptor leads to increased aggressiveness in mice, reports Rene Hen of the Institut de Chimie Biologique in Strasbourg, France.

Hen and his colleagues created "knockout" mice, genetically engineered animals that lack the gene for the 5HT1b receptor. These animals don't produce the receptor, enabling researchers0 to study serotonin in new ways. Previous pharmacological studies often confronted by the variety of similar serotonin receptors, explain Hen. This made it difficult to interpret exactly which receptors responded to any given drug.

"These knockout mice develop, feed, and mate normally, but when challenged in aggression tests, [they] show a clear-cut difference in their behavior," Hen says. When confronted with an intruder, the mutant mice attacked faster, more often, and more intensely than their normal cousins. Moreove, the mutant mice showed less anxiety under stress, Hen reports.

These results confirm earlier studies suggesting that his receptor is a molecular target through which serotonin controls aggression, he states.

"We know there is a link between aggression and decreased [concentrations of] serotonin in humans as well. Knocking out the serotonin receptor has the same effect as reducing serotonin [concentrations]," he says. There is no evidence suggesting that mutations in seroptonin receptors are a major cause of abnormal aggression in humans, he adds.