PET studies of the effect of the antidepressant drugs nefazodone or paroxetine on [¹¹C]raclopride binding in human brain

Serotonin modulates dopamine release in the striatum. In this study we set out to determine whether nefazodone and paroxetine, two antidepressant drugs that interact with the brain serotonin system, produce detectable changes in synaptic dopamine in vivo in the human brain using positron emission tomography (PET) and [¹¹C]raclopride, a dopamine D-2 receptor specific radiotracer that is sensitive to changes in synaptic dopamine. Three normal healthy human volunteers had 4 PET/[¹¹C]raclopride scans each in 2 sessions. In the first session, subjects had a baseline [¹¹C]raclopride scan and a second scan 1 hour following the oral administration of either nefazodone (200 mg PO) or paroxetine (20 mg PO). Four to 6 weeks later, in a second PET/[¹¹C]raclopride session, the same subjects received the other drug for comparison. Neither nefazodone nor paroxetine produced significant changes in [¹¹C]raclopride binding. This and other reports in the literature indicate that different drugs that affect the serotonin system do not produce consistent and predictable changes in [¹¹C]raclopride binding and that a full understanding of their actions on serotonin and the associated changes in dopamine requires further investigation.