Our primary hypothesis is that the intravenous use of an alpha(2) antagonist in patients with major depression during REM sleep will activate the LC and thus increase noradrenergic activity during a time when the LC is normally quiescent- namely REM sleep. If the hypothesis that it is the timing of the activation of the noradrenergic system that is crucial in the antidepressant effect of sleep deprivation is correct then an acute antidepressant effect should be observed in patients despite minimal to no disruption of sleep.