Prenatal SSRI alters the hormonal and behavioral responses to stress in female mice: Possible role for glucocorticoid resistance.
Life time prevalence of major depression disorder (MDD) is higher in women compared to men especially during the period surrounding childbirth. Women suffering from MDD during pregnancy use antidepressant medications, particularly Selective Serotonin Reuptake Inhibitors (SSRI). These drugs readily cross the placental barrier and impact the developing fetal brain. The present study assessed the effects of prenatal exposure to fluoxetine (FLX), an SSRI antidepressant drug, on corticosterone and behavioral responses to stress in female mice. In young females, prenatal FLX significantly elevated corticosterone response to continuous stress. In adults, prenatal FLX augmented corticosterone response to acute stress and suppressed the response to continuous stress. Additionally, prenatal FLX significantly augmented stress-induced increase in locomotion and reduced anxiety- and depressive-like behaviors in adult, but not young mice. The dexamethasone suppression test revealed that prenatal FLX induced a state of glucocorticoid resistance in adult females, indicating that the negative feedback control of the hypothalamic-pituitary-adrenal axis response to stress was disrupted. These findings provide the first indication of altered hormonal and behavioral responses to continuous stress and suggest a role for the development of glucocorticoid resistance in these effects. According to these findings, prenatal environment may have implications for stress sensitivity and responsiveness to life challenges. Furthermore, this study may assist in understanding the limitations and precautions that should be taken in the use of SSRIs during pregnancy.
School of Behavioral Sciences, The Academic College of Tel Aviv-Yaffo, Tel Aviv, Israel. Electronic address: avitsur@mta.ac.il.
Ronit
R
Avitsur
School of Behavioral Sciences, The Academic College of Tel Aviv-Yaffo, Tel Aviv, Israel.
Rachel
R
Grinshpahet
School of Behavioral Sciences, The Academic College of Tel Aviv-Yaffo, Tel Aviv, Israel.
Naama
N
Goren
School of Behavioral Sciences, The Academic College of Tel Aviv-Yaffo, Tel Aviv, Israel.
Ido
I
Weinstein
School of Behavioral Sciences, The Academic College of Tel Aviv-Yaffo, Tel Aviv, Israel.
Or
O
Kirshenboim
School of Behavioral Sciences, The Academic College of Tel Aviv-Yaffo, Tel Aviv, Israel.
Noa
N
Chlebowski
D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000503:physiopathology; D008661:Metabolism, Inborn Errors / Q000139:chemically induced* / Q000503:physiopathology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000503:physiopathology*; D011965:Receptors, Glucocorticoid / Q000172:deficiency*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013315:Stress, Psychological / Q000097:blood / Q000503:physiopathology*
D003345:Corticosterone; D005473:Fluoxetine; D011965:Receptors, Glucocorticoid; D017367:Selective Serotonin Reuptake Inhibitors
Fluoxetine; Glucocorticoid resistance; HPA axis; Major depression disorder; Restraint stress; SSRI