"Our results are very exciting because they establish that low serotonin could be a contributing factor to the development of depression in response to psycho-social stress in a genetically defined animal model of serotonin deficiency," said senior author Marc Caron from Duke University's School of Medicine in the US.

Following exposure to stress, the serotonin-deficient mice also did not respond to a standard anti-depressant fluoxetine (Prozac), which works by boosting serotonin transmission between neighbouring neurons.

The new results may help explain why some people with depression seem unresponsive to treatment with selective serotonin re-uptake inhibitors (SSRIs), the most common anti-depressant drugs on the market today.

In the new study, researchers used a transgenic mouse strain called Tph2KI that has only 20-40 percent of normal levels of serotonin in its brain. These mice harbour an extremely rare mutation that was first identified in a small group of people with major depression.

The researchers tested the responses of these mice to a type of psycho-social stress: social defeat stress. The team stressed out mice by housing them each with an aggressive stranger mouse briefly every day for 7-10 days.

Later, the scientists examined whether the test mice would avoid interacting with an unfamiliar mouse - a depression-like behaviour. A week of social stress was not sufficient for normal mice to show signs of depression, but the serotonin-deficient mice did.

The study appeared in the journal Proceedings of the National Academy of Sciences.


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