Effect of Long-time Postnatal Exposure to Sevoflurane on Causing Attention-deficit/Hyperactivity Disorder in Rats

Abstract

To investigate whether long-term exposure to inhaled sevoflurane, a volatile anesthetic, causes abnormal activities and memory impairment related to attention-deficit/hyperactivity disorder (ADHD) in neonatal rats. On postnatal day 5 (P5), Sprague-Dawley rats were randomly assigned to two sevoflurane subgroups and two control subgroups and underwent experimental intervention. The two sevoflurane (SEVO) subgroups were exposed to 3% sevoflurane for 2 h and 4 h respectively, while the two control subgroups were given pure oxygen for the same amount and duration. Behavioral tests, including open-field test (OFT), five-choice serial reaction time task (5-CSRTT), fear-conditioning (FC) and Morris water maze (MWM), were applied to evaluate changes in cognition, memory, anxiety and ADHD-related behavioral changes in the rats in adolescence (-P25) and in adulthood (-P65). In OFT, the SEVO 2 h and SEVO 4 h subgroups displayed activity level and exploratory behaviors similar to those of the control subgroups on P21 and P61, with no statistically significant difference identified in the data. 5-CSRTT results on P25 and P65 indicated no statistically significant difference between the SEVO subgroups and the control subgroups in regard to ADHD-related abnormal behaviors, including number of immature reaction, rate of correct response and omission rate. In the FC experiment, SEVO 4 h group had a shorter freezing period and longer period of freezing latency ( P=0.029) in comparison to the control groups. The results of the MWM test showed that the escape latency period of rats in the SEVO 4 h group was significantly prolonged on the second day and the third day, compared to the control groups ( P<0.05). The average swimming speed of SEVO groups did no exhibit any statistically significant difference on P69 or P76. The time the SEVO 4 h group spent in the target quadrant was significantly shorter than that of the control group ( P=0.039) and percentage of distance traveled in the target quadrant was significantly reduced compared to that the control group ( P=0.048). The findings suggest that four hours of inhaled sevoflurane exposure in neonate rats may cause memory impairment, but does no increase risks for ADHD-related abnormal activities.