Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Blocker ZD7288 Prevents Sevoflurane-Induced Hyperactivity in a Novel Mice Behavioral Model

Background: Besides effect of general anesthesia, sevoflurane also induces hyperactivity during induction and recovery, especially in young children. Lack of satisfied animal model impedes the investigation of causes of the hyperactivity as well as its prevention. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker might produce sedative effect. This study developed a novel mice model of hyperactive behaviors and further explored effects of HCN channel blocker on sevoflurane-induced hyperactivity.  Methods: C57BL/6 mice were used in the present study. Maximal speed, mean speed, total movement distance and resting percentage of mice were quantitatively measured by behavioral tracking software. Age-dependence of this model was also analyzed. HCN channel blocker ZD7288 at doses of 6.25 and 12.5 μg/kg were intraperitoneal injected to prevent sevoflurane-induced hyperactivity. Results: In the behavioral model, sevoflurane could induce significant hyperactivity in mice under 1% sevoflurane inhalation and in recovery period, characterized as increased movement speed and total distance. The sevoflurane-induced hyperactivity was more significant in young mice than adult (P<0.01). Pre-administration of ZD7288 could significantly prevent sevoflurane-induced hyperactivity. Conclusions: The mice behavioral model developed in this study could characterize sevoflurane-induced hyperactivity in induction and recovery period as well as age-dependence. In addition, by this animal model, HCN channel blocker ZD7288 could prevent sevoflurane-induced hyperactivity. Thus, HCN channel might be the underlying therapeutic target for sevoflurane-induced agitation in general anesthesia.   Citation: Peng Liang, Xu-Bin Huang, Feng-Shan Li, Han Huang, Jing-Xuan Qiu, Da-Qing Liao, et al. Hyperpolarization-activated cyclic nucleotide-gated channel blocker ZD7288 prevents sevoflurane-induced hyperactivity in a novel mice behavioral model. J Anesth Perioper Med 2017; 4: 205-12. doi: 10.24015/JAPM.2017.0011This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.