The effects of perinatal fluoxetine treatment on the circadian system of the adult mouse

Abstract

Rational: Depression is prevalent among women of childbearing age and is frequently treated with selective serotonin reuptake inhibitors (SSRIs). As some SSRIs, such as fluoxetine (Flx), can cross the placenta, it is possible that the neurodevelopment of the fetus may be affected, leading to altered behavior in adulthood.

Objectives: In this study, we examined the effects of perinatal Flx exposure on the subsequent expression of circadian rhythms in adult mice.

Methods: Dams were treated with 25 mg/kg/day Flx in their drinking water from embryonic day 15 to postnatal day 12. Circadian organization of wheel running rhythms and phase shifts to photic and non-photic stimuli were assessed in the offspring starting at 6 weeks of age.

Results: We found that perinatal Flx exposure led to larger light-induced phase advances (1.19 ± 0.51 vs. 0.55 ± 0.25 h), smaller phase advances to the serotonin agonist 8-OH-DPAT during the mid-subjective day (0.44 ± 0.15 vs. 0.70 ± 0.17 h), and a shorter free-running period in constant darkness (23.47 ± 0.13 vs. 23.64 ± 0.13 h).

Conclusions: These results suggest that perinatal exposure to SSRIs may have consequences for the functioning of the circadian system later in life.