Neonatal Exposure to Sevoflurane Induces Abnormal Social Behaviors and Deficits in Fear Conditioning in Mice

• Published in: Anesthesiology (Philadelphia) Vol. 110; no. 3; pp. 628 - 637
• Main Authors: SATOMOTO, Maiko, SATOH, Yasushi, TERUI, Katsuo, MIYAO, Hideki, TAKISHIMA, Kunio, ITO, Masataka, IMAKI, Junko
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-03-2009
• Subjects: Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Animals, Newborn; Biological and medical sciences; Conditioning (Psychology) - drug effects; Conditioning (Psychology) - physiology; Fear - drug effects; Fear - physiology; Fear - psychology; Learning Disorders - chemically induced; Learning Disorders - physiopathology; Learning Disorders - psychology; Male; Medical sciences; Memory Disorders - chemically induced; Memory Disorders - physiopathology; Memory Disorders - psychology; Methyl Ethers - adverse effects; Mice; Mice, Inbred C57BL; Social Behavior; Volatile compound; Human; Rodentia; Sevoflurane; Fear; Vertebrata; Mammalia; Newborn; General anesthetic; Mouse; Animal; Anesthesia; Conditioning; Halogen Organic compounds
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/aln.0b013e3181974fa2

Neonatal exposure to anesthetics that block N-methyl-D-aspartate receptors and/or hyperactivate gamma-aminobutyric acid type A receptor has been shown to cause neuronal degeneration in the developing brain, leading to functional deficits later in adulthood. The authors investigated whether exposure of neonatal mice to inhaled sevoflurane causes deficits in social behavior as well as learning disabilities.
Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 6 h. Activated cleaved caspase-3 immunohistochemical staining was used for detection of apoptosis. Cognitive functions were tested by pavlovian conditioned fear test. Social behavior was tested by social recognition and interaction tests.
Neonatal exposure to sevoflurane significantly increased the number of apoptotic cells in the brain immediately after anesthesia. It caused persistent learning deficits later in adulthood as evidenced by decreased freezing response in both contextual and cued fear conditioning. The social recognition test demonstrated that mice with neonatal exposure to sevoflurane did not develop social memory. Furthermore, these mice showed decreased interactions with a social target compared with controls in the social interaction test, indicating a social interaction deficit. The authors did not attribute these abnormalities in social behavior to impairments of general interest in novelty or olfactory sensation, because they did not detect significant differences in the test for novel inanimate object interaction or for olfaction.
This study shows that exposure of neonatal mice to inhaled sevoflurane could cause not only learning deficits but also abnormal social behaviors resembling autism spectrum disorder.