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2755199 
Journal Article 
Serotonin Transporter Occupancy in Rats Exposed to SSRIs in Utero or via Breast Milk 
Owens, MJ; Capello, C; Goren, D; Stowe, ZN 
2004 
1 
Neuropsychopharmacology
ISSN: 0893-133X
EISSN: 1740-634X 
DART/TER/4002338 
29 
Suppl 1 
English 
Studies have begun to examine prenatal and/or post partum exposure of human infants to SSRIs. However, information regarding CNS effects such as neonatal CNS clearance post delivery or the impact of exposure via breast milk on CNS receptor occupancy is unknown. In many instances, SSRI concentrations in infants are below the limits of detection utilizing standard analytic techniques. Nevertheless, infants are exposed to trace concentrations of SSRIs which are hypothesized to partially inhibit the SERT. Rats were exposed to SSRIs in utero or postnatally via breast milk at doses that mimic serum concentrations observed in human investigations (median and ~85th percentile). Dam and pup serum drug concentrations were assayed by HPLC. Fresh frozen brains were sectioned and ex vivo autoradiography was performed using 125I-RTI55. E21 rat pups exposed to paroxetine or sertraline during the final 10 days of pregnancy exhibited ~80% or and gt;95% occupancy, respectively, at delivery at both doses. By postnatal day 4, occupancy had significantly decreased. In a second group of rats, naive pups were exposed to paroxetine or sertraline via breast milk. Despite undetectable pup serum concentrations, the higher dose of both paroxetine and sertraline resulted in 30-50% SERT occupancy in 4 day old rat brains. Fine motor skills were assessed in adult rats exposed to an SSRI in utero using a beam traversing task for 5 consecutive days. Female rats exposed to an SSRI in utero performed worse than their vehicle control counterparts on day 5. In these preliminary studies, male rats also performed worse but less so than the females. SSRIs have proven extremely valuable in the treatment of pregnant and nursing women, nevertheless further modeling of drug exposure in infants combined with CNS measures will enhance guidelines which can be used to systematically minimize fetal and neonatal medication exposure.