Of Mice and Bullies: Scientists Help Rodents Cope

Scientists have tinkered with the genes in mice brains to help them cope with depression and stress.

The alterations work just as well as giving the rodents antidepressant medications normally prescribed to humans, a new study shows.

The research could eventually lead to new treatments for depressed people.

10 days of bullying

Mice are generally social animals, and they frequently introduce themselves to unfamiliar mice.  But if exposed to daily bouts of "social defeat," such as being beat up a stranger, a mouse will stop approaching unfamiliar mice.

Scientists subjected mice to 10 straight days of such bullying and found that the defeated mice avoided bullies even four weeks after their initial beating.

In fact, they were so traumatized that they avoided all other mice as well—even those that were smaller and more docile.

"For both mice and men, social status is important; for mice, losing to a dominant mouse usually means that they avoid the dominant and they avoid social situations," said Thomas Insel of the National Institute of Mental Health.

When researchers gave the mice the human antidepressant drugs Prozac or Tofranil, social interaction improved. The treatment resembled that for depressed humans, said the study's senior author Eric Nestler of the University of Texas Southwestern Medical Center.

Scientists noticed that defeated mice had increased amounts of a gene called BDNF in a region of their brains involved in social memory. BDNF helps regulate the neurotransmitter dopamine, a chemical that carries signals from one nerve cell to another along the brain's reward pathway.

By removing this gene, researchers found mice could be bullied endlessly and not become depressed or socially withdrawn.

"Removal of BDNF before bullying, or treatment with antidepressants after bullying, both removed the behavioral abnormality observed," Nestler told LiveScience.

Help for humans?

Lacking this response, however, could make these mice more susceptible to being bullied in the wild.

"Without BDNF in the circuit, an animal can't learn that a social stimulus is threatening and respond appropriately," Nestler said.

Despite this and other possible negative effects of totally inhibiting BDNF, the research could lead to new antidepressant drugs for humans.

"The challenge is to find a way to inhibit BDNF signaling within the reward pathway specifically," Nestler said. "The many genes we show that are regulated by BDNF or antidepressants in this pathway may provide clues."

This research is detailed in the Feb. 10 issue of the journal Science.

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