Examining the Reversibility of Long-Term Behavioral Disruptions in Progeny of Maternal SSRI Exposure
| العنوان: | Examining the Reversibility of Long-Term Behavioral Disruptions in Progeny of Maternal SSRI Exposure |
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| المؤلفون: | Adrian M. Corbett, Krystal C. Chandler, Katherine B. McCullough, Susan E. Maloney, Joseph D. Dougherty, Michael A. Rieger, Shyam K. Akula, Audrey E. McGowin |
| المصدر: | eNeuro |
| بيانات النشر: | Society for Neuroscience, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, Offspring, Autism Spectrum Disorder, Serotonin reuptake inhibitor, autism, Serotonergic, social behavior, 03 medical and health sciences, Mice, 0302 clinical medicine, Pregnancy, medicine, SSRI, Animals, CELF Proteins, 030304 developmental biology, 0303 health sciences, Fluoxetine, Behavior, Animal, business.industry, General Neuroscience, fluoxetine, Age Factors, 3.1, General Medicine, New Research, medicine.disease, serotonin, Mice, Inbred C57BL, Disease Models, Animal, Autism spectrum disorder, Prenatal Exposure Delayed Effects, Autism, Disorders of the Nervous System, Female, Serotonin, business, sensory sensitivity, Neuroscience, 030217 neurology & neurosurgery, Selective Serotonin Reuptake Inhibitors, medicine.drug |
| الوصف: | Visual Abstract 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. |
| اللغة: | English |
| تدمد: | 2373-2822 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b0d2b24b05547c98ed5475a118699d67Test http://europepmc.org/articles/PMC6071194Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b0d2b24b05547c98ed5475a118699d67 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23732822 |
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