Mice overcome fear with 'Prozac'
2008-10-09 08:29
Washington - The brain can produce
antidepressants with the right signal, a finding that suggests
that meditating, or going to your "happy place" truly works,
scientists reported on Wednesday.
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.
The experiment suggests that there are good ways to teach
people this skill, and points to new routes for developing
better antidepressants, said Dr Eric Kandel of the Howard
Hughes Medical Institute and Columbia University in New York,
who led the research.
"The happy place works. This is like going to the country,"
Kandel said in a telephone interview.
Writing in the journal Neuron, Kandel's team said they used
classical conditioning to train mice.
Reverse study
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.
"It scares the hell out of the animal," Kandel said.
They decided to reverse the study - they played 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.
To make a mouse depressed, they used a method favoured by
drug companies called learned helplessness.
"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."
New pathways
Further experiments showed the tone and an antidepressant
drug worked synergistically, he said.
When they looked at the brains of their mice, they saw
using the conditioned "safety" tone activated a different
pathway than the drugs did.
It affected dopamine, 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.
The learned safety did not affect serotonin.
Mice conditioned by the "safety" tone also had more newborn
brain cells in the dentate gyrus, a part of the brain linked
with learning and depression.
Radiation
When Kandel's team used radiation to slow the birth of new
cells in the dentate gyrus, the effects of learned safety and
of antidepressants were blunted.
Kandel noted that antidepressant drugs appear to work, in
part, by encouraging the growth of new brain cells - as does
psychotherapy.
"Learning involves alterations in the brain and gene
expression," Kandel said. "Psychotherapy is only a form of
learning."
This shows how effective psychotherapy, meditation and
other stress-reduction tools may be, and it could help in the
design of new drugs, Kandel said.
"This opens up new pathways that may profitable," he said.