Neonatal Exposure to Citalopram Selectively Alters the Expression of the Serotonin Transporter in the Hippocampus: Dose‐Dependent Effects

• Published in: Anatomical record (Hoboken, N.J. : 2007) N.J. : 2007), 2010-11, Vol.293 (11), p.1920-1932
• Main Authors: Weaver, Kristin J., Paul, Ian A., Lin, Rick C.S., Simpson, Kimberly L.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; antidepressant; Caudate Nucleus - drug effects; Caudate Nucleus - embryology; Caudate Nucleus - metabolism; Cerebral Cortex - physiology; Citalopram - pharmacology; Cognition - physiology; development; dorsal raphe; Dose-Response Relationship, Drug; Female; Hippocampus - drug effects; Hippocampus - embryology; Hippocampus - metabolism; Models, Animal; Pregnancy; Prenatal Exposure Delayed Effects - metabolism; Putamen - drug effects; Putamen - embryology; Putamen - metabolism; Rats; Rats, Long-Evans; reuptake inhibitor; serotonin; Serotonin Plasma Membrane Transport Proteins - metabolism; Serotonin Uptake Inhibitors - pharmacology; Ventral Thalamic Nuclei - drug effects; Ventral Thalamic Nuclei - embryology; Ventral Thalamic Nuclei - metabolism
• ISSN: 1932-8486; 1932-8494; 1932-8494
• DOI: 10.1002/ar.21245

Infants born to mothers taking selective serotonin reuptake inhibitors (SSRIs) late in pregnancy have been reported to exhibit signs of antidepressant withdrawal. Such evidence suggests that these drugs access the fetal brain in utero at biologically significant levels. Recent studies in rodents have revealed that early exposure to antidepressants can lead to long lasting abnormalities in adult behaviors, and result in robust decreases in the expression of a major serotonin synthetic enzyme (tryptophan hydroxylase) along the raphe midline. In the present investigation, we injected rat pups with citalopram (CTM: 5 mg/kg, 10 mg/kg, and 20 mg/kg) from postnatal Days 8–21, and examined serotonin transporter (SERT) labeling in the hippocampus, ventrobasal thalamic complex, and caudate‐putamen when the subjects reached adulthood. Our data support the idea, that forebrain targets in receipt of innervation from the raphe midline are particularly vulnerable to the effects of CTM. SERT‐immunoreactive fiber density was preferentially decreased throughout all sectors of the hippocampal formation, whereas the subcortical structures, each supplied by more lateral and rostral aspects of the raphe complex, respectively, were not significantly affected. Reductions in SERT staining were also found to be dose‐dependent. These findings suggest that SSRIs may not only interfere with the establishment of chemically balanced circuits in the neonate but also impose selective impairment on higher cortical function and cognitive processes via more circumscribed (i.e., regionally specific) deficits in 5‐HT action. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.