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

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.

Our aim was to investigate the effects of perinatal exposure to the SSRI fluoxetine (FLX) on circadian behavior, affective behavior, and 5-HT_1A receptor sensitivity in female rats. In addition, we studied the expression of clock genes and the 5-HT_1A receptor in the SCN, as they are potentially involved in underlying mechanisms contributing to changes in circadian rhythms.

Perinatal FLX exposure shortened the free-running tau in response to the 5-HT_1A/7 agonist 8-OH-DPAT. However, FLX exposure did not alter anxiety, stress coping, and 5-HT_1A receptor sensitivity. No differences were found in 5-HT_1A receptor and clock genes Per1, Per2, Cry1, and Cry2 SCN gene expression.

Perinatal FLX exposure altered the response to a phase-shifting challenge in female rats, whether this may pose health risks remains to be investigated.