October 9, 2008
Test Mice Show How Brain Produces Natural Antidepressant
Scientists reported on Wednesday that the brain can produce antidepressants with the right kind of signal, a finding that suggests that meditating, or going to your "happy place," truly works.
Researchers discovered lab mice forced to swim endlessly until they surrendered and just floated, waiting to drown, could be conditioned to regain their will to live when a tone they associated with safety was played.
Dr. Eric Kandel of the Howard Hughes Medical Institute and Columbia University in New York, who led the research, said the experiment suggests that there are good ways to teach people this skill, and points to new routes for developing better antidepressants.
"The happy place works. This is like going to the country," Kandel said.
Kandel's team used classical conditioning to train mice. They had already conditioned some mice to fear a neutral tone by playing the sound when they shocked the animals' paws. After a while, the tone itself creates fear.
Kandel said it scares the hell out of the animal.
The team then decided to reverse the study, playing the tone when they were not shocking the mice. "It learned that the only time it was really safe is when the tone comes on," Kandel said.
They used a method favored by drug companies called learned helplessness to make a mouse depressed.
"You put an animal into a pool of water and it can't get out. It gives up and it stops swimming and it just floats," Kandel said.
"When you give the animal an antidepressant, it starts swimming again. When we played the tone, it started to swim again just as it did with the antidepressant."
He said further experiments showed the tone and an antidepressant drug worked synergistically.
The researchers noticed that in the brains of their mice, they saw using the conditioned "safety" tone activated a different pathway than the drugs did.
Dopamine levels were affected, while antidepressants work on serotonin. Both are message-carrying molecules called neurotransmitters.
The conditioning also affected a compound called brain-derived neurotrophic factor or BDNF -- which helps nourish and encourages the growth of brain cells.
However, the learned safety did not affect serotonin.
Those test mice conditioned with the "safety" tone also had more newborn brain cells in the dentate gyrus, a part of the brain linked with learning and depression.
When radiation was used to slow the birth of new cells in the dentate gyrus, the effects of learned safety and of antidepressants were blunted.
Antidepressant drugs appear to work, in part, by encouraging the growth of new brain cells -- as does psychotherapy, Kandel noted.
"Learning involves alterations in the brain and gene expression," Kandel said. "Psychotherapy is only a form of learning."
Kandel said this shows how effective psychotherapy, meditation and other stress-reduction tools may be, and it could help in the design of new drugs.
He believes the results could open up new pathways that may profitable.
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