Veronika Kiryanova1,2, Victoria M Smith1,2, Richard H Dyck1,2,3, Michael C Antle4,5,6. 1. Department of Psychology, University of Calgary, Calgary, AB, T2N 1N4, Canada. 2. Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. 3. Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB, Canada. 4. Department of Psychology, University of Calgary, Calgary, AB, T2N 1N4, Canada. antlem@ucalgary.ca. 5. Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. antlem@ucalgary.ca. 6. Department of Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada. antlem@ucalgary.ca.
Abstract
INTRODUCTION: Women of child-bearing age are the population at greatest risk for depression. The stress experienced during pregnancy and the associated antidepressant treatments can both affect fetal development. Fluoxetine (FLX) is among the most common antidepressants used by pregnant women. We have previously demonstrated that perinatal exposure to FLX can alter expression of circadian rhythms in adulthood. Here, we examine the combined effects of maternal stress during pregnancy and perinatal exposure to the antidepressant FLX on the circadian behavior of mice as adults. METHODS: Mouse dams were exposed to chronic unpredictable stress (embryonic (E) day 7 to E18), FLX (E15 to postnatal day 12), a combination of both stress and FLX, or were left untreated. At 2 months of age, male offspring were placed in recording chambers and circadian organization of wheel running rhythms and phase shifts to photic and non-photic stimuli were assessed. RESULTS: Mice exposed to prenatal stress (PS) had smaller light-induced phase delays. Mice exposed to perinatal FLX required more days to re-entrainment to an 8-h phase advance of their light-dark cycle. Mice subjected to either perinatal FLX or to PS had larger light-induced phase advances and smaller phase advances to 8-OH-DPAT. FLX treatment partially reversed the effect of PS on phase shifts to late-night light exposure and to 8-OH-DPAT. CONCLUSIONS: Our results suggest that, in mice, perinatal exposure to either FLX, or PS, or their combination, leads to discernible, persistent changes in their circadian systems as adults.
INTRODUCTION:Women of child-bearing age are the population at greatest risk for depression. The stress experienced during pregnancy and the associated antidepressant treatments can both affect fetal development. Fluoxetine (FLX) is among the most common antidepressants used by pregnant women. We have previously demonstrated that perinatal exposure to FLX can alter expression of circadian rhythms in adulthood. Here, we examine the combined effects of maternal stress during pregnancy and perinatal exposure to the antidepressant FLX on the circadian behavior of mice as adults. METHODS:Mouse dams were exposed to chronic unpredictable stress (embryonic (E) day 7 to E18), FLX (E15 to postnatal day 12), a combination of both stress and FLX, or were left untreated. At 2 months of age, male offspring were placed in recording chambers and circadian organization of wheel running rhythms and phase shifts to photic and non-photic stimuli were assessed. RESULTS:Mice exposed to prenatal stress (PS) had smaller light-induced phase delays. Mice exposed to perinatal FLX required more days to re-entrainment to an 8-h phase advance of their light-dark cycle. Mice subjected to either perinatal FLX or to PS had larger light-induced phase advances and smaller phase advances to 8-OH-DPAT. FLX treatment partially reversed the effect of PS on phase shifts to late-night light exposure and to 8-OH-DPAT. CONCLUSIONS: Our results suggest that, in mice, perinatal exposure to either FLX, or PS, or their combination, leads to discernible, persistent changes in their circadian systems as adults.
Authors: Danielle J Houwing; Jolien de Waard; Anouschka S Ramsteijn; Tom Woelders; Sietse F de Boer; Emma J Wams; Jocelien D A Olivier Journal: Psychopharmacology (Berl) Date: 2020-06-12 Impact factor: 4.530