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

by
Heurteaux C, Lucas G, Guy N, El Yacoubi M, Thummler S, Peng XD, Noble F, Blondeau N, Widmann C, Borsotto M, Gobbi G, Vaugeois JM, Debonnel G, Lazdunski M. [1] Institut de Pharmacologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS), Universite de Nice Sophia Antipolis, Institut Paul Hamel, 660 Route des Lucioles, Sophia-Antipolis, 06560 Valbonne, France. [2] These authors contributed equally to this work.
Nat Neurosci. 2006 Aug 13;


ABSTRACT

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(-/-)) 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.
CREB1
5-HT1a
Options
21st century
Antidepressants
Transcriptomics
Pharmacogenetics
5-HT1a and anxiety
Proteomics and the CNS
Depression and nerve cell death

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