Social stress in mice is controlled by genetic pathway, researchers find

Deleting a specific gene in the brain has the same effect that antidepressants do in mice that have been conditioned to be depressed, report researchers at UT Southwestern Medical Center.

Mice are normally social animals, easily approaching and greeting unfamiliar mice. But when the strange mice are aggressive, a mouse over time becomes timid and withdrawn. Administering antidepressants such as Prozac improves their behavior, but so does deleting a gene called BDNF.

UT Southwestern researchers say conditioning mice to be withdrawn provides a new model for researching not only depression, but also other human ailments such as social phobia and post-traumatic stress disorder. In addition, deleting the BDNF gene can help track a biochemical pathway of depression in the brain, the researchers report in the Feb. 10 issue of the journal Science.

"This study provides new evidence of the importance of reward pathways in the brain in an animal's responses to social stress, and by extension to depression. It also provides some insight into the underlying molecular events involved," said Dr. Eric J. Nestler, chairman of psychiatry the study's senior author.

Dr. Nestler and his colleagues exposed mice to daily bouts of "social defeat," in which they encountered aggressive mice that overcame them in fights. This training went on for 10 days. The mice eventually became "defeated," no longer approaching unfamiliar mice. Even four weeks later, the defeated mice avoided other mice, not only their former bullies but even smaller and more docile mice.

When given the antidepressant drugs Prozac or Tofranil, the defeated mice's social interaction improved. The importance of the antidepressant use was that it worked over a long period, not just short-term, thus resembling human treatment, Dr. Nestler said.

"It's been hard for researchers to find a condition in animals that responds to chronic administration of antidepressants," he said.

Contact: Aline McKenzie
UT Southwestern Medical Center

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