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Rodent of the week: Mice who aren't scaredy cats

October 10, 2008 |  8:05 am

Rodent of the week A classic way that researchers teach mice to be afraid is to sound a tone and immediately follow it with a small electric shock to their paws. Scientists can then study what fear and anxiety do to the brain. It doesn't take long before the mice become anxious and afraid at the sound of the tone, even without the follow-up shock.

Recently, though, scientists have found that they can teach mice a kind of calm fearlessness, even in a stressful situation, getting from them the same response as, say, a dose of Prozac. "It's a little bit like psychotherapy," Eric Kandel said in a news release. He's the lead author of a study in the Oct. 8 journal Neuron, and an investigator at the Howard Hughes Medical Institute. "This shows that behavioral intervention works."

Here's what they did. They taught mice learned safety, pairing a tone with uneventful calmness and safety. These mice learned to associate the tone with absence of danger.

Then it was into the little mouse swimming pool for everyone, normally a pretty stressful situation for any critter who can't figure out how to get out of the water. The swimming mice, not surprisingly, normally become desperate. Earlier research has shown that antidepressants help rodents remain calm, even in the stressful swimming pool.

The new experiment showed that mice who had gone through learned-safety training remained calm, even in the swimming pool.

"In this seemingly desperate situation –- where the mice have no option to escape from the water -- they start to show signs of behavioral despair that are ameliorated by antidepressant medications. We found that the mice trained for safety could overcome their sense of hopelessness in the swim test," Kandel explained.

The antidepressant effect in the safety-conditioned mice was similar and comparable in magnitude to treatment with the drug fluoxetine (Prozac), Kandel noted in the release.

After analyzing the brains of the mice who had been through safety training, researchers were intrigued to find that the training did not affect serotonin, the brain chemical targeted by many antidepressants. Rather, learned safety affected dopamine and neuropeptide neurotransmitters, suggesting new targets for antidepressant drug development.

-- Susan Brink