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Long‐term consequences of neonatal fluoxetine exposure in adult rats
Author(s) -
Ko MengChing,
Lee Lukas JyuhnHsiarn,
Li Yang,
Lee LiJen
Publication year - 2014
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.22185
Subject(s) - prefrontal cortex , basolateral amygdala , amygdala , serotonin , endocrinology , fluoxetine , gestation , medicine , serotonin reuptake inhibitor , dendritic spine , neuroscience , limbic system , biology , hippocampus , fetus , antidepressant , central nervous system , hippocampal formation , pregnancy , receptor , genetics , cognition
ABSTRACT Serotonin (5‐HT) plays important roles during neural development. Administration of selective serotonin reuptake inhibitor (SSRI)‐type medication during gestation may influence the maturation of the fetal brain and subsequent brain functions. To mimic the condition of late‐gestation SSRI exposure, we administered fluoxetine (FLX) in neonatal rats during the first postnatal week, which roughly corresponds to the third trimester period of human gestation. FLX‐exposed adult male rats exhibited reduced locomotor activity and depression‐like behaviors. Furthermore, sensorimotor gating capacity was also impaired. Interestingly, increased social interaction was noticed in FLX‐exposed rats. When the levels of 5‐HT and tryptophan hydroxylase were examined, no significant changes were found in FLX rats compared to control (CON) rats. The behavioral phenotypes of FLX rats suggested malfunction of the limbic system. Dendritic architectures of neurons in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) were examined. Layer II/III mPFC pyramidal neurons in FLX rats had exuberant dendritic branches with elongated terminal segments compared to those in CON rats. In BLA pyramidal neurons, the dendritic profiles were comparable between the two groups. However, in FLX rats, the density of dendritic spines was reduced in both mPFC and BLA. Together, our results demonstrated the long‐lasting effects of early FLX treatment on emotional and social behaviors in adult rats in which impaired neuronal structure in the limbic system was also noticed. The risk of taking SSRI‐type antidepressants during pregnancy should be considered. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1038–1051, 2014

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