Combined effect of maternal serotonin transporter genotype and prenatal stress in modulating offspring social interaction in mice

• Published in: International journal of developmental neuroscience 2010-10, Vol.28 (6), p.529-536
• Main Authors: Jones, Karen L., Smith, Ryan M., Edwards, Kristin S., Givens, Bennet, Tilley, Michael R., Beversdorf, David Q.
• Format: Article
• Language: English
• Subjects: Animal model; Animals; Animals, Newborn; Anxiety; Anxiety - physiopathology; Autism; Behavior, Animal; Female; Genotype; Knockout mouse; Maternal Behavior; Mice; Mice, Inbred C57BL; Mice, Knockout; Pregnancy; Prenatal Exposure Delayed Effects - physiopathology; Prenatal stress; Serotonin Plasma Membrane Transport Proteins - genetics; Serotonin transporter; Social Behavior; Stress
• ISSN: 0736-5748; 1873-474X
• DOI: 10.1016/j.ijdevneu.2010.05.002

Several studies suggest that prenatal stress is a possible risk factor in the development of autism spectrum disorders. However, many children exposed to stress prenatally are born healthy and develop typically, suggesting that other factors must contribute to autism. Genes that contribute to stress reactivity may, therefore, exacerbate prenatal stress‐mediated behavioral changes in the adult offspring. One candidate gene linked to increased stress reactivity encodes the serotonin transporter. Specifically, an insertion/deletion (long/short allele) polymorphism upstream of the serotonin transporter gene correlates with differential expression and function of the serotonin transporter and a heightened response to stressors. Heterozygous serotonin transporter knockout mice show reductions in serotonin transporter expression similar to the human short polymorphism. In this study, the role of prenatal stress and maternal serotonin transporter genotype were assessed in mice to determine whether their combined effect produces reductions in social behavior in the adult offspring. Pregnant serotonin transporter heterozygous knockout and wild‐type dams were placed in either a control condition or subjected to chronic variable stress. The adult offspring were subsequently assessed for social interaction and anxiety using a three‐chamber social approach task, ultrasonic vocalization detection, elevated‐plus maze and an open field task. Results indicated that prenatal stress and reduced serotonin transporter expression of the dam may have the combined effect of producing changes in social interaction and social interest in the offspring consistent with those observed in autism spectrum disorder. This data indicates a possible combined effect of maternal serotonin transporter genotype and prenatal stress contributing to the production of autistic‐like behaviors in offspring.