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Int J Clin Exp Pathol 2011;4(2):162-168

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).

Keywords: SSRI, dendritic spine density, neuronal development, fluoxetine, fluvoxamine

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Address all correspondence to:
Dr. Rui Wang
School of Pharmacy, East China University of Science and Technology
130 Meilong Road, Shanghai 200237, P.R. China.
Tel: 86-21-64250608, Fax: 86-21-64250608