Neuron 65, 40–52 (2010)

Many antidepressants increase levels of the neurotransmitter serotonin in the brain. But the drugs don't work in all patients. It has been suggested that a particular gene variant of the human serotonin receptor 5-HT1A increases the risk of depression and decreases response to treatment. Where these receptors occur on serotonin-releasing neurons they function as 'autoreceptors', inhibiting serotonin release when levels rise.

René Hen of Columbia University in New York and his colleagues have developed a mouse model in which they can control the levels of these autoreceptors without affecting the other type of 5-HT1A receptor.

Mice with high autoreceptor levels behaved in a manner typical of depression when subjected to stress, and their behaviour was unaltered by long-term treatment with the antidepressant fluoxetine. However, when their autoreceptor levels were lowered before treatment, they responded to the drug.