Serotonin transporter occupancy in rats exposed to serotonin reuptake inhibitors in utero or via breast milk

Catherine F. Capello, Chase H. Bourke, James C. Ritchie, Zachary N. Stowe, Donald J Newport, Amanda Nemeroff, Michael J. Owens

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Rigorous data regarding fetal central nervous system (CNS) exposure after antidepressant exposure are sparse. The magnitude of serotonin reuptake inhibitor (SRI) CNS exposure was measured in three groups of rats using ex vivo autoradiography of the serotonin transporter (SERT): 1) in utero, 2) postnatal clearance after birth, and 3) exposure through lactation. Rats were exposed to one of five SRI-type antidepressants (escitalopram, fluoxetine, paroxetine, sertraline, and venlafaxine) administered continuously via osmotic minipumps to pregnant or nursing dams. Dam dosing was adjusted to reflect the 50th and 85th percentiles of serum concentrations observed in pregnant women. Embryonic day 21 rat pups exposed in utero exhibited >80% SERT occupancy in brain tissue, which is equivalent to that of the pregnant dam and similar to that reported for human pharmacotherapy. Venlafaxine was the exception with occupancies ranging from 61 to 92% across different litters. The magnitude of SERT occupancy is essentially equivalent between dams and fetuses. By postnatal day 4, high SERT occupancy was observed only in fluoxetine-exposed pups (41-92% occupancy). Significantly less, but measurable, exposure occurred via breast milk exposure even in the absence of detectable drug concentrations in nursing pup sera. Pups exposed to SRIs via breast milk for 3 or 7 days exhibited varying SERT occupancies (0-57% depending on the individual medication and dam dose). These data highlight the need for animal modeling of fetal and nursing infant drug exposure using clinically meaningful dosing strategies and appropriate CNS measures to develop rational treatment guidelines that systematically minimize fetal and neonatal medication exposure in humans.

Original languageEnglish (US)
Pages (from-to)275-285
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume339
Issue number1
DOIs
StatePublished - Oct 2011
Externally publishedYes

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Serotonin Uptake Inhibitors
Human Milk
Nursing
Central Nervous System
Fluoxetine
Antidepressive Agents
Sertraline
Paroxetine
Citalopram
Autoradiography
Serum
Lactation
Pharmaceutical Preparations
Pregnant Women
Fetus
Parturition
Guidelines
Drug Therapy
Brain

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Serotonin transporter occupancy in rats exposed to serotonin reuptake inhibitors in utero or via breast milk. / Capello, Catherine F.; Bourke, Chase H.; Ritchie, James C.; Stowe, Zachary N.; Newport, Donald J; Nemeroff, Amanda; Owens, Michael J.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 339, No. 1, 10.2011, p. 275-285.

Research output: Contribution to journalArticle

Capello, Catherine F. ; Bourke, Chase H. ; Ritchie, James C. ; Stowe, Zachary N. ; Newport, Donald J ; Nemeroff, Amanda ; Owens, Michael J. / Serotonin transporter occupancy in rats exposed to serotonin reuptake inhibitors in utero or via breast milk. In: Journal of Pharmacology and Experimental Therapeutics. 2011 ; Vol. 339, No. 1. pp. 275-285.
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