Abstract: Abstract: Objective To investigate the effect of dexmedetomidine (Dex) preconditioning on the long-term synaptic plasticity damage induced by repeated exposure of sevoflurane in neonatal rats. Methods Forty-eight rats were randomly assigned into sevoflurane group (group S), sevoflurane preconditioning group (group DS) and control group (group C), with 16 rats in each group. Rats in group S were intraperitoneally injected with 3 mL/kg normal saline before inhaling sevoflurane for 4 h at d7, d14 and d21. Rats in group DS were injected intraperitoneally with 20 μg/kg Dex dissolved in 3 mL/kg normal saline before 4 h sevoflurane inhalation at the same time points. Rats in group C inhaled carrier gas for 4 h after injecting 3 mL/ kg normal saline. Eight rats were randomly selected from each group at d37 and d97 to detect learning and memory ability by Morris water maze. Thereafter, in vivo electrophysiological experiments were implemented to compare the longterm potentiation (LTP) and paired-pulse facilitation (PPF) ratio in hippocampal neurons between three groups. Results At both juvenile and adult rats, comparing with rats in group C and group DS, the escape latency was remarkably prolonged in rats of group S, and the number of crossing through the target quadrant was reduced (P＜0.05). The increments of field excitatory postsynaptic potential (fEPSP) slope at all time points after high frequency stimulation were remarkably lower in rats of group S than those of group C and group DS (P＜0.05), while PPF ratio was significantly higher at multiple stimulus intervals in group S than group C and group DS (P＜0.05). As compared to group S at juvenile age, the escape latency at adult age was shortened in the first and second day in group S, and the number of crossing was increased. Meanwhile in the group S at adult age, the increment of fEPSP after high frequency stimulation was higher, and the PPF ratios induced by paired stimulation with interstimulus interval of 50 ms,100 ms,150 ms and 200 ms were obviously lower than those of group S at juvenile age (P＜0.05). Conclusion Dexmedetomidine can ameliorate the abnormal changes on the long-term and shortterm synaptic plasticity, as well as learning and memory ability, which could provide a new strategy for prevention and treatment of adverse effects on the developing brain induced by sevoflurane in clinical practice.

Key words: dexmedetomidine, neuronal plasticity, synapses, sevoflurane, learning and memory ability