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Prenatal selective serotonin reuptake inhibitor (SSRI) exposure induces working memory and social recognition deficits by disrupting inhibitory synaptic networks in male mice

Cited 2 time in Web of Science Cited 2 time in Scopus
Authors
Yu, Weonjin; Yen, Yi-Chun; Lee, Young-Hwan; Tan, Shawn; Xiao, Yixin; Lokman, Hidayat; Ting, Audrey Khoo Tze Ting; Ganegala, Hasini; Kwon, Taejoon; Ho, Won-Kyung; Je, H. Shawn
Issue Date
2019-04-01
Citation
Molecular Brain, 12(1):29
Keywords
PrenatalSerotonin (5-HT)Selective serotonin reuptake inhibitorSSRIFluoxetineWorking memorySocial recognitionSerotonin 2A receptor (5-HT2AR)
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressant drugs in pregnant women. Infants born following prenatal exposure to SSRIs have a higher risk for behavioral abnormalities, however, the underlying mechanisms remains unknown. Therefore, we examined the effects of prenatal fluoxetine, the most commonly prescribed SSRI, in mice. Intriguingly, chronic in utero fluoxetine treatment impaired working memory and social novelty recognition in adult males. In the medial prefrontal cortex (mPFC), a key region regulating these behaviors, we found augmented spontaneous inhibitory synaptic transmission onto the layer 5 pyramidal neurons. Fast-spiking interneurons in mPFC exhibited enhanced intrinsic excitability and serotonin-induced excitability due to upregulated serotonin (5-HT) 2A receptor (5-HT2AR) signaling. More importantly, the behavioral deficits in prenatal fluoxetine treated mice were reversed by the application of a 5-HT2AR antagonist. Taken together, our findings suggest that alterations in inhibitory neuronal modulation are responsible for the behavioral alterations following prenatal exposure to SSRIs.
ISSN
1756-6606
Language
English
URI
http://hdl.handle.net/10371/153142
DOI
https://doi.org/10.1186/s13041-019-0452-5
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Physiology (생리학교실)Journal Papers (저널논문_생리학교실)
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