Original Article Neonatal exposure to fluoxetine and fluvoxamine alteres spine density in mouse hippocampal CA1 pyramidal neurons
Jing Zheng, Da-Feng Xu1, Kui Li, Hong-Tao Wang, Peng-Cheng Shen, Min Lin, Xiao-Hua Cao, Rui Wang
School of Pharmacy, East China University of Science and Technology, Shanghai, China; Laboratorory of Synaptic Plasticity and Learning Behavior, Shanghai Institute of Brain Functional Genomics, East China Normal University, Shanghai 200062, China.
Received December 9, 2010; accepted January 3, 2011; January 5, 2011; published February 1, 2011
Abstract: Some women in childbearing ages take selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and fluvoxamine as antidepressants. However, these compounds caused 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 densities of CA1 neurons. We found that 18-day drug applications of fluoxetine and fluvoxamine significantly resulted in reduced spine densities of basal dendrites at postnatal day 22 (P22), but only fluvoxamine caused a reduction of spine densities of apical dendrites. Interestingly, compared with the control group, the spine densities of basal dendrites after fluoxetine and fluvoxamine exposure and the spine densities of apical dendrites after fluoxetine exposure were higher in adult mice at the age of P90. We also observed impaired locomotor activities 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. (IJCEP1012005).
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