Acute changes in cerebrospinal fluid 5-HIAA following oral paroxetine challenge in healthy humans

Abstract

A number of studies have reported decreased human lumbar cerebrospinal fluid (CSF) concentrations of the major serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), following chronic administration of selective serotonin reuptake inhibitors (SSRIs). Thisdecrease has been thought to be a consequence of elevated extracellular serotonin and to be mediated through terminalautoreceptorfeedback inhibition of serotonin turnover. We wished to study the previously unexamined acute effects of SSRI administration on humanCSF 5-HIAA. A seriallumbar puncture (LP) procedure was used to collect CSF samples before and after a single oral40 mg dose of theSSRI paroxetine (PAR) or matching placebo in eight healthy adult humans in a randomized, double-blind fashion. CSF 5-HIAAconcentrations did not change following placebo, but showed a statistically significant 27% mean increase 3 h following PAR. Our findingsstand in contrast to the decreases reported for CSF 5-HIAA after chronic SSRI treatment in humans and the decreases seen in brainextracellular 5-HIAA after acute or chronic administration of SSRIs to animals. © 2003 Nature Publishing Group.