Selective serotonin reuptake inhibitor treatment of early postnatal mice reverses their prenatal stress-induced brain dysfunction.
Prenatal stress has long-lasting effects on cognitive function and on the hypothalamic-pituitary-adrenal response to stress. We previously reported that the serotonin concentration and synaptic density in the hippocampus were reduced following prenatal stress [Int J Dev Neurosci 16 (1998) 209]. Since serotonin plays a role in the formation and maintenance of synapses, we hypothesized that a neonatal reduction in hippocampal serotonin levels may lead to learning disabilities in prenatally stressed mice. To test this hypothesis, we treated prenatally stressed mice with a selective serotonin reuptake inhibitor in order to normalize their postnatal serotonin turnover levels. What we found was that the oral administration of a selective serotonin reuptake inhibitor to prenatally stressed mice during postnatal weeks 1-3 but not 6-8 normalized their corticosterone response to stress, serotonin turnover in the hippocampus, and density of dendritic spines and synapses in the hippocampal CA3 region. Concomitantly, such treatment partially restored their ability to learn spatial information.
Ishiwata
H
H
Department of Anatomy, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.
Shiga
T
T
Okado
N
N
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D015306:Biogenic Monoamines / Q000378:metabolism; D001927:Brain Diseases / Q000188:drug therapy* / Q000209:etiology; D002452:Cell Count / Q000379:methods; D003345:Corticosterone / Q000097:blood; D049229:Dendritic Spines / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D004924:Escape Reaction / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000473:pathology; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission / Q000379:methods; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017966:Pyramidal Cells / Q000473:pathology; D011930:Reaction Time / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013312:Stress, Physiological / Q000150:complications / Q000188:drug therapy*; D013569:Synapses / Q000473:pathology / Q000648:ultrastructure
D015306:Biogenic Monoamines; D003345:Corticosterone; D017367:Selective Serotonin Reuptake Inhibitors