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Epidemiological studies suggest exposures to anesthetic agents and/or sedative drugs (AASDs) in children under three years old, or pregnant women during the third trimester, may adversely afect brain development. Evidence suggests lengthy or repeated AASD exposures are associated with increased risk of neurobehavioral defcits. Animal models have been valuable in determining the type of acute damage in the developing brain induced by AASD exposures, as well as in elucidating long-term functional consequences. Few studies examining very early exposure to AASDs suggest this may be a critical period for inducing long-term functional consequences, but the impact of repeated exposures at these ages has not yet been assessed. To address this, we exposed mouse pups to a prototypical general anesthetic, isofurane (ISO, 1.5% for 3hr), at three early postnatal ages (P3, P5 and P7). We quantifed the acute neuroapoptotic response to a single versus repeated exposure, and found age- and brain region-specifc efects. We also found that repeated early exposures to ISO induced subtle, sex-specifc disruptions to activity levels, motor coordination, anxiety-related behavior and social preference. Our fndings provide evidence that repeated ISO exposures may induce behavioral disturbances that are subtle in nature following early repeated exposures to a single AASD.

Publication Date

January 2019

Publication Title

Scientific Reports

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Psychology Commons



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