Chronic exposure of female mice to selective serotonin reuptake inhibitors during lactation induces vocal behavior deficits in pre-weaned offspring

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Abstract

Developmental factors for autism spectrum disorders (ASDs) have been an ongoing debate despite an increasing number of reports on genetic factors. Recent studies have suggested maternal intake of selective serotonin reuptake inhibitors (SSRIs) as a possible developmental factor elevating the risk for ASD in offspring. Here, we show that maternal exposure of mice to an SSRI, Fluoxetine (FLX), induces abnormal ultrasonic vocalizations (USVs), an indicator of ASD-related behavior. We tested the effect of FLX intake during pregnancy, lactation, or both. We found that the lactation and both conditions decreased the number of USVs emitted by offspring pups. An index for assessing the syllables' frequency modulation revealed that highly modulated syllables appeared to be inhibited only in both conditions. Furthermore, we found that the number of serotonergic neurons at adulthood was reduced in the progeny of mice treated with FLX in all conditions. In addition, maternal exposure to FLX through pregnancy and lactation induced a high death rate of early post-natal pups. These suggest that the maternal exposure to SSRIs affects early development of offsprings as well as the serotonergic system. Focusing on vocal communication, our results indicate that intake of an SSRI during lactation increases the risk of abnormal USVs in pups, and provides potential insights into the development of ASD.

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Lan, Z., Tachibana, R. O., & Kanno, K. (2023). Chronic exposure of female mice to selective serotonin reuptake inhibitors during lactation induces vocal behavior deficits in pre-weaned offspring. Pharmacology Biochemistry and Behavior, 230. https://doi.org/10.1016/j.pbb.2023.173606

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