Anesthetic sevoflurane could induce neurotoxicity in developing brain and cause adverse neurobehavioral outcomes in mice, including inattention, social interaction deficit, and learning and memory impairment. However, there is less data on the effect of anesthesia plus surgery on social interaction behavior. Therefore, we investigated whether the combination of anesthesia and surgical stimulation could induce behavioral and biochemical changes in mice. Firstly, the six-day-old mice were received either 3% sevoflurane anesthesia or abdominal surgery under sevoflurane anesthesia. Then, these mice were scheduled to social interaction test in three-chambered social paradigm at one-month-old. In addition, the brain tissues of neonatal mice were harvested at 24 h after treatment, for measuring the levels of OXTR and NMDAR1 in Western blot analysis. We found that neonatal anesthesia with sevoflurane in a clinically-relevant dosage could not induce social interaction deficit. Nevertheless, anesthesia plus surgery was able to impair preference for social novelty in mice. Moreover, anesthesia plus surgery decreased the levels of OXTR in hippocampus and cortex of mice, as well as NMDAR1 in hippocampus. Collectively, these results suggested that anesthesia plus surgery could impair social novelty preference, but not sociability in mice, and that social memory might be more vulnerable than social affiliation in biological property. Furthermore, reduction in the levels of cortex OXTR and hippocampus NMDAR1 could be associated with social recognition memory in mice.

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