RT Journal Article
SR Electronic
T1 Examining the Reversibility of Long-Term Behavioral Disruptions in Progeny of Maternal SSRI Exposure
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0120-18.2018
DO 10.1523/ENEURO.0120-18.2018
VO 5
IS 4
A1 Susan E. Maloney
A1 Shyam Akula
A1 Michael A. Rieger
A1 Katherine B. McCullough
A1 Krystal Chandler
A1 Adrian M. Corbett
A1 Audrey E. McGowin
A1 Joseph D. Dougherty
YR 2018
UL http://www.eneuro.org/content/5/4/ENEURO.0120-18.2018.abstract
AB Serotonergic dysregulation is implicated in numerous psychiatric disorders. Serotonin plays widespread trophic roles during neurodevelopment; thus perturbations to this system during development may increase risk for neurodevelopmental disorders. Epidemiological studies have examined association between selective serotonin reuptake inhibitor (SSRI) treatment during pregnancy and increased autism spectrum disorder (ASD) risk in offspring. It is unclear from these studies whether ASD susceptibility is purely related to maternal psychiatric diagnosis, or if treatment poses additional risk. We sought to determine whether maternal SSRI treatment alone or in combination with genetically vulnerable background was sufficient to induce offspring behavior disruptions relevant to ASD. We exposed C57BL/6J or Celf6 +/- mouse dams to fluoxetine (FLX) during different periods of gestation and lactation and characterized offspring on tasks assessing social communicative interaction and repetitive behavior patterns including sensory sensitivities. We demonstrate robust reductions in pup ultrasonic vocalizations (USVs) and alterations in social hierarchy behaviors, as well as perseverative behaviors and tactile hypersensitivity. Celf6 mutant mice demonstrate social communicative deficits and perseverative behaviors, without further interaction with FLX. FLX re-exposure in adulthood ameliorates the tactile hypersensitivity yet exacerbates the dominance phenotype. This suggests acute deficiencies in serotonin levels likely underlie the abnormal responses to sensory stimuli, while the social alterations are instead due to altered development of social circuits. These findings indicate maternal FLX treatment, independent of maternal stress, can induce behavioral disruptions in mammalian offspring, thus contributing to our understanding of the developmental role of the serotonin system and the possible risks to offspring of SSRI treatment during pregnancy.