TREK1 is a widely expressed background potassium channel. Similar to mice treated with selective serotonin reuptake inhibitors (SSRIs), TREK1 knockout mice are resistant to depression-like behavior and have elevated serotonin levels leading to speculation that TREK1 inhibition may contribute to the therapeutic effects of SSRIs. This study examined how chronic fluoxetine administration and a common functional polymorphism in the serotonin-transporter-linked promoter region (5-HTTLPR) influence cortical TREK1 expression in 24 rhesus monkeys. The short rh5-HTTLPR allele as well as female gender were associated with reduced cortical TREK1 protein expression but chronic SSRI administration had no effect. These results suggest that serotonin may influence TREK1, but that chronic SSRI treatment does not result in long lasting changes in cortical TREK1 protein expression. TREK1 gender differences may be related to gender differences in serotonin and require further research.
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