title: Neonatal exposure to fluoxetine and fluvoxamine alteres spine density in mouse hippocampal CA1 pyramidal neurons.
abstract: Some women in childbearing ages take selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and fluvoxamine for treating psychiatric symptoms. However, these compounds may cause some side effects to their children. It has been identified that early life exposure to SSRIs increased the chance of developing mood disorders and the biological basis is still unclear. Here, we studied the effects of neonatal exposure to SSRIs on neuronal morphology. We used GFP-transgenic mice to investigate the acute and long-lasting effects of early life exposure to SSRIs on dendritic spine density of CA1 neurons. We found that 18-day drug applications of fluoxetine and fluvoxamine significantly reduced spine density of basal dendrites at postnatal day 22 (P22), but only fluvoxamine caused a reduction of spine density of apical dendrites. Interestingly, compared with the control group, the spine densities of basal dendrites after fluoxetine and fluvoxamine exposure and the spine density of apical dendrites after fluoxetine exposure increased in adult mice at the age of P90. We also observed impaired locomotor activity in adult mice after exposure to SSRIs. Our findings demonstrated that neonatal exposure to SSRIs was capable of influencing the morphological plasticity of excitatory synapses. It raised the caution for clinical use of SSRIs.
authors.affiliation: School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.forename: Da-Feng
authors.initials: DF
authors.lastname: Xu
authors.forename: Kui
authors.initials: K
authors.lastname: Li
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Wang
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Shen
authors.forename: Min
authors.initials: M
authors.lastname: Lin
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Cao
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D003712:Dendrites / Q000187:drug effects* / Q000473:pathology; D005106:Exploratory Behavior / Q000187:drug effects; D005473:Fluoxetine / Q000633:toxicity*; D016666:Fluvoxamine / Q000633:toxicity*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects* / Q000473:pathology; D017367:Selective Serotonin Reuptake Inhibitors / Q000633:toxicity*
chemical_list: D005473:Fluoxetine; D016666:Fluvoxamine; D017367:Selective Serotonin Reuptake Inhibitors