Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

Mol Brain. 2019 04 1 ;12(1):29. Epub 2019 Apr 1. PMID: 30935412

Abstract Author(s):

Weonjin Yu, Yi-Chun Yen, Young-Hwan Lee, Shawn Tan, Yixin Xiao, Hidayat Lokman, Audrey Khoo Tze Ting, Hasini Ganegala, Taejoon Kwon, Won-Kyung Ho, H Shawn Je

Article Affiliation:

Weonjin Yu


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-HTR) signaling. More importantly, the behavioral deficits in prenatal fluoxetine treated mice were reversed by the application of a 5-HTR antagonist. Taken together, our findings suggest that alterations in inhibitory neuronal modulation are responsible for the behavioral alterations following prenatal exposure to SSRIs.

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