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Kwon, Taejoon
TaejoonLab
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  • Systems biology, computational biology, functional genomics

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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

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Title
Prenatal selective serotonin reuptake inhibitor (SSRI) exposure induces working memory and social recognition deficits by disrupting inhibitory synaptic networks in male mice
Author
Yu, WeonjinYen, Yi-ChunLee, Young-HwanTan, ShawnXiao, YixinLokman, HidayatTing, Audrey Khoo TzeGanegala, HasiniKwon, TaejoonHo, Won-KyungJe, H. Shawn
Issue Date
2019-04
Publisher
BMC
Citation
MOLECULAR BRAIN, v.12, pp.29
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.
URI
https://scholarworks.unist.ac.kr/handle/201301/26909
URL
https://molecularbrain.biomedcentral.com/articles/10.1186/s13041-019-0452-5
DOI
10.1186/s13041-019-0452-5
ISSN
1756-6606
Appears in Collections:
SLS_Journal Papers
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