Perinatal antidepressant exposure alters cortical network function in rodents

• Published in: Proceedings of the National Academy of Sciences - PNAS 2011-11, Vol.108 (45), p.18465-18470
• Main Authors: Simpson, Kimberly L, Weaver, Kristin J, de Villers-Sidani, Etienne, Lu, Jordan Y.-F, Cai, Zhengwei, Pang, Yi, Rodriguez-Porcel, Federico, Paul, Ian A, Merzenich, Michael, Lin, Rick C. S
• Format: Article
• Language: English
• Subjects: Animals; Antidepressants; Antidepressive Agents, Second-Generation - pharmacology; Autism; Autistic disorder; Autistic Disorder - physiopathology; Axons; Behavior, Animal; Behavioral neuroscience; Biological Sciences; Brain; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cerebral Cortex - physiology; citalopram; Drugs; early development; Female; Fetuses; Homeostasis; humans; Immunohistochemistry; Infants; Information processing; Male; Myelin; myelin sheath; Neophobia; Neural networks; Neurons; Perinatal exposure; play activities; pups; Rats; Rodents; Sensory integration; Serotonin; Serotonin - metabolism; Serotonin agents; Serotonin receptors; Serotonin uptake inhibitors; Serotonin Uptake Inhibitors - pharmacology; Somatosensory cortex
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1109353108

Serotonin (5-HT) plays a key role in early brain development, and manipulation of 5-HT levels during this period can have lasting neurobiological and behavioral consequences. It is unclear how perinatal exposure to drugs, such as selective serotonin reuptake inhibitors (SSRIs), impacts cortical neural network function and what mechanism(s) may elicit the disruption of normal neuronal connections/interactions. In this article, we report on cortical wiring organization after pre- and postnatal exposure to the SSRI citalopram. We show that manipulation of 5-HT during early development in both in vitro and in vivo models disturbs characteristic chemoarchitectural and electrophysiological brain features, including changes in raphe and callosal connections, sensory processing, and myelin sheath formation. Also, drug-exposed rat pups exhibit neophobia and disrupted juvenile play behavior. These findings indicate that 5-HT homeostasis is required for proper brain maturation and that fetal/infant exposure to SSRIs should be examined in humans, particularly those with developmental dysfunction, such as autism.