Irwin Lucki, Ph.D., and colleagues from the University of Pennsylvania School of Medicine discovered that the neurotransmitter norepinephrine plays a more important role than previously thought in mediating the effects of common anti-depressant medications, including selective serotonin reuptake inhibitors (SSRIs).

Researchers tested the behavior effects of medications from different drug classes on mice genetically altered to be deficient in norepinephrine.They found that, compared to normal mice, the mice unable to synthesize norepinephrine did not respond to most antidepressants. Although scientists previously assumed that the serotonergic system was the crucial target for SSRIs, this study shows that their effects can also depend on responses from the noradrenergic system. Findings from this study confirm other reports suggesting that SSRIs may be "selective" only at their initial target of action; subsequent effects of these medications require multiple neurotransmitter systems including norepinephrine.