Serotonin Transporter Binding Potentials in Brain of Juvenile Monkeys 1 Year After Discontinuation of a 2-Year Treatment With Fluoxetine

Abstract

Background: The potential long-term effects of childhood fluoxetine therapy on brain serotonin systems were studied using a nonhuman primate model, the rhesus monkey.

Methods: Juvenile male rhesus (1-4 years of age, corresponding to 4-11 years of age in children) were treated orally with fluoxetine (2 mg/kg) or vehicle daily for 2 years and removed from treatment during the third year. Each treatment group was assigned an equal number of subjects with low and high transcription polymorphisms of MAOA. One year after discontinuation of treatment, positron emission tomography scans were conducted (n = 8 treated monkeys, n = 8 control monkeys) using [¹¹C]DASB to quantify serotonin transporter in 16 cortical and subcortical regions.

Results: Fluoxetine-treated monkeys with MAOA low transcription polymorphism had significantly lower [¹¹C]DASB binding potentials than control monkeys. This finding was seen throughout the brain but was strongest in prefrontal and cingulate cortices. The MAOA × fluoxetine interaction was enhanced by binding potentials that were nonsignificantly higher in monkeys with high transcription polymorphism.

Conclusions: Juvenile fluoxetine treatment has residual posttreatment effects on brain serotonin transporter that depend on MAOA genotype. MAOA genotype may be important to consider when treating children with fluoxetine.

Keywords: Fluoxetine; Juvenile; MAOA polymorphism; PET; Rhesus monkey; Serotonin transporter.