Fluoxetine during development reverses the effects of prenatal stress on depressive-like behavior and hippocampal neurogenesis in adolescence

• Published in: PloS one 2011-09, Vol.6 (9), p.e24003
• Main Authors: Rayen, Ine, van den Hove, Daniël L, Prickaerts, Jos, Steinbusch, Harry W, Pawluski, Jodi L
• Format: Article
• Language: English
• Subjects: Adolescence; Adolescents; Analysis; Animals; Antidepressants; Antidepressive Agents - administration & dosage; Antidepressive Agents - adverse effects; Antidepressive Agents - therapeutic use; Anxiety; Anxiety - chemically induced; Behavior; Behavior, Animal - drug effects; Behavior, Animal - physiology; Biology; Body Weight - drug effects; Brain research; Breastfeeding & lactation; Cardiomyopathy; Cell proliferation; Child development; Childhood mental disorders; Depression (Mood disorder); Depression - chemically induced; Depression - drug therapy; Exposure; Female; Females; Fetus - physiology; Fluoxetine; Fluoxetine - administration & dosage; Fluoxetine - adverse effects; Fluoxetine - therapeutic use; Hippocampus; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - growth & development; Immunohistochemistry; Ki-67 Antigen - metabolism; Laboratories; Male; Maternal Behavior - drug effects; Maternal Exposure - adverse effects; Medicine; Mental depression; Mental health; Microtubule-Associated Proteins - metabolism; Neurogenesis; Neurogenesis - drug effects; Neuropeptides - metabolism; Neurosciences; Offspring; Open-field behavior; Perinatal exposure; Postpartum; Pregnancy; Pregnant women; Prenatal experience; Psychological aspects; Psychopharmacology; Rats; Rats, Sprague-Dawley; Rodents; Serotonin; Serotonin uptake inhibitors; Serotonin Uptake Inhibitors - administration & dosage; Serotonin Uptake Inhibitors - adverse effects; Serotonin Uptake Inhibitors - therapeutic use; Stress; Stress, Physiological - drug effects; Stresses; Studies; Swimming; Teenagers
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0024003

Depression during pregnancy and the postpartum period is a growing health problem, which affects up to 20% of women. Currently, selective serotonin reuptake inhibitor (SSRIs) medications are commonly used for treatment of maternal depression. Unfortunately, there is very little research on the long-term effect of maternal depression and perinatal SSRI exposure on offspring development. Therefore, the aim of this study was to determine the role of exposure to fluoxetine during development on affective-like behaviors and hippocampal neurogenesis in adolescent offspring in a rodent model of maternal depression. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle beginning on postnatal day 1 (P1). Adolescent male and female offspring were divided into 4 groups: 1) prenatal stress+fluoxetine exposure, 2) prenatal stress+vehicle, 3) fluoxetine exposure alone, and 4) vehicle alone. Adolescent offspring were assessed for anxiety-like behavior using the Open Field Test and depressive-like behavior using the Forced Swim Test. Brains were analyzed for endogenous markers of hippocampal neurogenesis via immunohistochemistry. Results demonstrate that maternal fluoxetine exposure reverses the reduction in immobility evident in prenatally stressed adolescent offspring. In addition, maternal fluoxetine exposure reverses the decrease in hippocampal cell proliferation and neurogenesis in maternally stressed adolescent offspring. This research provides important evidence on the long-term effect of fluoxetine exposure during development in a model of maternal adversity.