Perinatal fluoxetine exposure disrupts the circadian response to a phase-shifting challenge in female rats

Danielle J. Houwing, Jolien de Waard, Anouschka S. Ramsteijn, Tom Woelders, Sietse F. de Boer, Emma J. Wams, Jocelien D.A. Olivier*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Rationale: Selective serotonin reuptake inhibitor (SSRI) antidepressants are increasingly prescribed during pregnancy. Changes in serotonergic signaling during human fetal development have been associated with changes in brain development and with changes in affective behavior in adulthood. The suprachiasmatic nucleus (SCN) is known to be modulated by serotonin and it is therefore assumed that SSRIs may affect circadian rhythms. However, effects of perinatal SSRI treatment on circadian system functioning in the offspring are largely unknown. Objective: Our aim was to investigate the effects of perinatal exposure to the SSRI fluoxetine (FLX) on circadian behavior, affective behavior, and 5-HT1A receptor sensitivity in female rats. In addition, we studied the expression of clock genes and the 5-HT1A receptor in the SCN, as they are potentially involved in underlying mechanisms contributing to changes in circadian rhythms. Results: Perinatal FLX exposure shortened the free-running tau in response to the 5-HT1A/7 agonist 8-OH-DPAT. However, FLX exposure did not alter anxiety, stress coping, and 5-HT1A receptor sensitivity. No differences were found in 5-HT1A receptor and clock genes Per1, Per2, Cry1, and Cry2 SCN gene expression. Conclusions: Perinatal FLX exposure altered the response to a phase-shifting challenge in female rats, whether this may pose health risks remains to be investigated.

Original languageEnglish
Pages (from-to)2555-2568
Number of pages14
Issue number8
Early online date12 Jun 2020
Publication statusPublished - Aug 2020


  • 5-HT1A receptor
  • Anxiety
  • Circadian behavior
  • Clock genes
  • Coping style
  • Fluoxetine
  • Hypothermia
  • Perinatal
  • Pregnancy


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