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Nature Neuroscience 9, 1134–1141 (1 September 2006) | doi:10.1038/nn1749

Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype

Catherine Heurteaux , Guillaume Lucas , Nicolas Guy , Malika El Yacoubi , Susanne Th|[uuml]|mmler , Xiao-Dong Peng , Florence Noble , Nicolas Blondeau , Catherine Widmann , Marc Borsotto , Gabriella Gobbi , Jean-Marie Vaugeois , Guy Debonnel & Michel Lazdunski

Depression is a devastating illness with a lifetime prevalence of up to 20%. The neurotransmitter serotonin or 5-hydroxytryptamine (5-HT) is involved in the pathophysiology of depression and in the effects of antidepressant treatments. However, molecular alterations that underlie the pathology or treatment of depression are still poorly understood. The TREK-1 protein is a background K+ channel regulated by various neurotransmitters including 5-HT. In mice, the deletion of its gene (Kcnk2, also called TREK-1) led to animals with an increased efficacy of 5-HT neurotransmission and a resistance to depression in five different models and a substantially reduced elevation of corticosterone levels under stress. TREK-1–deficient (Kcnk2|[minus]|/|[minus]|) mice showed behavior similar to that of naive animals treated with classical antidepressants such as fluoxetine. Our results indicate that alterations in the functioning, regulation or both of the TREK-1 channel may alter mood, and that this particular K+ channel may be a potential target for new antidepressants.