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A Potential New Target For Antidepressants

 
  August, 16 2006 10:34
your information resource in human molecular genetics
 
     
A potassium channel called TREK1 may represent a new target for antidepressant drugs, according to research to be published in the September 2006 issue of Nature Neuroscience. The channel may exert its effects through a signaling pathway in the brain different to that normally targeted by most conventional antidepressants, which are thought to work by increasing the level of the neurotransmitter serotonin in the brain.

Michel Lazdunski and colleagues studied mice lacking the gene for the TREK1 channel, which normally contributes to the background currents that set the resting membrane potential of neurons. In several behavioral tests used to model depression, these mice behaved as if they had been treated with an antidepressant. In addition, they had increased serotonergic activity, and did not release as much of the stress hormone corticosterone as normal mice in response to mild stress. Moreover, the authors report that the TREK1 channel was also directly inhibited by conventional antidepressants.

The finding that mice lacking the gene for TREK1 behave as if they have been given an antidepressant suggests that small molecule 'blockers' of the potassium channel might be effective therapeutically. If TREK1 is found to exert its antidepressant effects through a pathway independent of serotonin, it is possible that future therapies targeting TREK1 channels may be faster acting and may have fewer side effects than conventional antidepressants.

Author contact:

Michel Lazdunski (Institut de Pharmacologie Moleculaire et Cellulaire, Sophia Antipolis, France)
E-mail: ipmc@ipmc.cnrs.fr

Abstract available online.

(C) Nature Neuroscience press release.


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