title: [TREK-1: a potential target for novel antidepressants].
abstract: The neurotransmitter serotonin (5-HT: 5-hydroxytryptamin) was suggested to be involved in the pathogenesis of depression as well as in the mechanisms of antidepressant treatments. However, the molecular mechanisms underlying the pathophysiology or treatment of depression are still poorly understood. A recent paper has shown that deletion of the two-pore domain potassium channel TREK-1 results in an antidepressant-like phenotype. TREK-1 -deficient mice behave as if they have been treated with an antidepressant drug, such as fluoxetine. Moreover, TREK-1-deficient mice showed a reduced elevation of corticosterone level under stress, an increased efficacy of 5-HT neurotransmission and an increased fluoxetine-induced neurogenesis in the hippocampus. Selective serotonin reuptake inhibitors (SSRIs) inhibited not only the 5-HT transporter but also the TREK-1 channel. In this article, we review the molecular and functional properties of the TREK-1 channel, which is a potential target for novel antidepressants.
authors: Department of Psychogeriatrics, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan. ymaru@ncnp.go.jp
authors: Yoshiaki
authors: Y
authors: Maruyama
authors: Mitsuhiko
authors: M
authors: Yamada
mesh_terms: D000818:Animals; D000928:Antidepressive Agents; D003863:Depression / Q000209:etiology; D015195:Drug Design; D005938:Glucocorticoids / Q000378:metabolism; D006624:Hippocampus; D006801:Humans; D051379:Mice; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013312:Stress, Physiological / Q000150:complications / Q000503:physiopathology
chemical_list: D000928:Antidepressive Agents; D005938:Glucocorticoids; D024683:Potassium Channels, Tandem Pore Domain; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C103742:potassium channel protein TREK-1