Exposure to prenatal antidepressant alters medial prefrontal-striatal synchronization in mice

Citalopram (CTM), a selective serotonin reuptake inhibitor (SSRI), has been widely used to treat panic disorders, such as depression which is one of the most disabling, yet common, psychiatric disorders. Although prenatal antidepressant exposure has a major impact on the neurobehavioral development of the offspring, such as anxiety, depression- and autism-like behaviors, the brain alterations of SSRI influence remained largely unknown. We show here, using electrophysiological recordings, that CTM exposure during the last 7 d of gestation can alter theta- and gamma-band oscillation and synchronization in the corticostriatal loop of 2-3 month-old mouse offspring. The dendritic length and number of dendritic branches in prefrontal neurons of these CTM-exposed mice are significantly reduced, consistent with decreased levels of N-methyl-d-aspartate receptors (NMDARs) and calcium/calmodulin-dependent protein kinase II (CaMKII) in the medial prefrontal cortex (mPFC). In addition, the level of c-Fos in both the mPFC and striatum is significantly increased. Together, these results advance our understanding of a neural network that is potentially responsible for abnormalities induced by prenatal antidepressant exposure.