| MECHANISM OF ACTION |
Findings by other researchers support this idea. Although serotonin and norepinephrine levels rise rapidly after a patient begins taking an antidepressant, "the onset of an appreciable clinical effect usually takes at least three to four weeks," note René Hen, an associate pharmacology professor at Columbia University, and colleagues in a Science paper [301, 805 (2003)]. The Hen team set out to provide evidence that the lag represents the time needed to grow new neurons in the hippocampus and that the growth is necessary for the antidepressants to work.
The researchers determined that mice in which hippocampal neurogenesis is prevented by X-ray damage do not respond to tricyclic or selective serotonin reuptake inhibitor (SSRI) antidepressants. They also studied mice lacking the gene to make the 5-HT1A serotonin receptor. When such mice--which are more anxious than normal mice--are treated with an SSRI antidepressant, their behavior doesn't improve, nor do they undergo neurogenesis. However, these mice show both behavioral improvements and neurogenesis in response to tricyclic antidepressants, which affect the neurotransmitter norepinephrine rather than serotonin.
|