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'Happy mice' to pave way for depression cure
Study involving genetically modified rodents will find a more effective medication, researchers say

Irwin Block, CanWest News Service
Published: Thursday, August 24, 2006

MONTREAL -- Successful experiments with genetically modified "happy" mice will open pathways for new medication to treat clinical depression, according to new research.

The experiments, conducted over two years in Montreal and Nice, France, showed that in stressful situations the genetically modified mice do not exhibit symptoms of depression, explained McGill University Health Centre psychiatrist Guy Debonnel.

The mice were bred without the Trek-1 gene, which affects transmission of serotonin in the brain. In various behavioural situations in the lab, these mice are found to be "non-depressive."

"When you put them in a bucket of water and they have no escape and can only swim or float, after a while normal mice will show signs of depression," said Debonnel, who is senior author of the research.

Normal mice "will just let go and not fight," but the genetically modified mice will continue swimming and never stop.

"To get the same kind of behaviour from a normal mouse you would have to treat it for three weeks with antidepressants," he said.

The deactivation of the gene, carried out at the University of Nice by research co-author Michel Lazdunski, had the effect of antidepressant treatment for the mice.

Another research method was to put an electrode in the mice's brain to record the activity of the serotonin system -- the neurotransmitter that is the target of most antidepressants currently on the market.

"We found that in these mice the electrical activity is two or three times higher than in normal mice," said Debonnel, adding this strengthened the conclusion that the absence of this gene is "like removing a brake on the serotonin system."

Almost all antidepressants on the market today -- the family known as SSRIs (selective serotonin reuptake inhibitors) -- work by regulating the flow of serotonin.

But these antidepressants do not work for about one-third of clinically depressed patients -- which is where this research offers some hope.

The research, published this week in Nature Neuroscience, indicates that a drug that blocks the Trek-1 gene and receptor in humans could be used to design an effective antidepressant, Debonnel noted.

"Industry is certainly working on Trek-1 receptors, but up to now there was no indication that these compounds might be interesting in treating depression," Debonnel said.

There is "a high level of homology" between the receptors of these rodents and those of humans, Debonnel said.

Health Canada and Statistics Canada report that about eight per cent of Canadians will suffer from depression at some point in their lives.

DEPRESSION FACTS

It's more common than you think.

8% of Canadians will suffer from depression at some point in their lifetime.

5% of Canadians seek medical advice for depression each year.

Source: Health Canada and Statistics Canada