Behavioral changes in developing mice after prenatal exposure to paroxetine (Paxil)

Am J Obstet Gynecol. 1999 Nov;181(5 Pt 1):1166-71. doi: 10.1016/s0002-9378(99)70102-x.

Abstract

Objective: The aim of this study was to conduct in a randomized, placebo-controlled manner behavioral testing on mice offspring exposed prenatally to the selective serotonin reuptake inhibitor paroxetine.

Study design: Forty-one CD-1 mice consumed paroxetine (Paxil, n = 21) or a placebo (n = 20) for 2 weeks before conception and throughout gestation. The daily dose of paroxetine used, 30 mg x kg(-1) x d(-1), is known to achieve concentrations in the rat serum equivalent to the upper therapeutic level in human beings and to achieve concentrations in the fetal rat brain equivalent to those in the adult mouse. Behavioral testing consisted of multiple tasks during early development, followed by motor, anxiety, reproduction, and depression tasks in the juvenile and adult periods.

Results: Offspring in the 2 treatment groups showed no statistical differences in many early development tasks (geotaxis, homing, social play) or in locomotor and exploratory activities throughout development. Performances during a depression task (forced swim), anxiety tasks (elevated plus maze as juveniles and adults), and reproduction revealed no treatment differences. Offspring exposed prenatally to paroxetine had a 15% to 25% increase in separation vocalization (P <.04) and a significant increase in male aggression during cage changing (P <.03).

Conclusion: Prenatal exposure to a clinically relevant dose of paroxetine in mice produced no major behavioral alterations but did heighten performance on select anxiety testing in infant offspring and on aggressive behavior in adult males.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression / drug effects
  • Animals
  • Animals, Newborn
  • Anxiety / chemically induced
  • Behavior, Animal / drug effects*
  • Body Weight / drug effects
  • Depression / chemically induced
  • Exploratory Behavior / drug effects
  • Female
  • Homing Behavior / drug effects
  • Litter Size / drug effects
  • Male
  • Maternal Exposure
  • Mice
  • Motor Activity / drug effects
  • Paroxetine / administration & dosage
  • Paroxetine / pharmacology*
  • Play and Playthings
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Random Allocation
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Sleep / drug effects
  • Time Factors
  • Vocalization, Animal / drug effects

Substances

  • Serotonin Uptake Inhibitors
  • Paroxetine