中文摘要：

目的观察N-甲基-D-天冬氨酸（NMDA）受体拮抗剂地革西平马来酸盐（MK-801）对小鼠感觉运动门控功能的影响，确定建立精神分裂症的感觉运动门控障碍小鼠模型的适宜剂量。方法采用不同剂量（0．125mg／kg、0．25mg／kg、0．50mg／kg）的MK-801建立感觉运动门控障碍的小鼠模型，用SR-LAB惊反射测试系统测定小鼠前脉冲抑制（PPI）、惊反射幅度和习惯化等行为学指标以比较不同剂量的药理作用。结果①前脉冲刺激的强度高于背景12dB时，MK-8010．125mg／kg、0．25mg／kg、0．50mg／kg各剂量组PPI的数值分别为（28．7％±4．8％）、（27．6％±5．6％）、（9．2％±4．0％），与对照组（53．6％±4．5％）的差异均有统计学意义（P〈0．01），呈剂量依赖性破坏了小鼠的PPI。②MK-801剂量为0．5mg／kg时，惊反射的幅度明显大于对照组（P〈0．001），增加的幅度为53％。③MK-8010．5mg／kg剂量组的习惯化为（-2．6％±10％），与正常对照组（43．7％±7．6％）相比，引起了习惯化明显损害（P〈0．001）。结论MK-801能够引起小鼠PPI的缺失，且能增加小鼠对惊反射刺激的反应性。0．50mg／kg的MK-801可作为建立精神分裂症的感觉运动门控障碍的小鼠模型的适宜剂量。

英文摘要：

Objective To investigate the effects of MK-801, a selective non-competitive N-methyl-D-aspartate （NMDA） receptor antagonist, on sensorimotor gating of mice and determine the appropriate dose for the deficient sensorimotor gating of schizophrenia model in mice. Methods Different doses of MK-801 （0. 125, 0. 25, 0. 50 mg/kg） were used to establish the schizophrenia model of deficient sensorimotor gating in mice. Prepulse inhibition （PPI）, startle ampli- tude and habituation in mice were measured using six SR-LAB startle chambers to determine the pharmacological actions of different doses of MK-801. Results ①At the 12dB prepulse level, the PPI in MK-801 at 0. 125, 0. 25 or 0. 50 mg/kg were （28.7% ±4. 8% ）, （27.5% ±5.6% ） or （9. 2% ±4.0% ）, respectively. Compared with the control group （53% ±4. 5% ）, MK-801 significantly disrupted PPI in a dose-dependent manner （P 〈0. 01 ）. ②MK-801 at the dose of 0. 50 mg/kg significantly increased the startle amplitude by 53% than the control group （P 〈 0. 001 ）. ③ The habituation of MK- 801 at 0. 50 mg/kg was （ -2.6% ± 10% ）. Compared with the control group, MK-801 （0. 50 mg/kg） impaired habitua- tion of the acoustic startle response （P 〈 0. 001 ）. Conchmions MK-801 induces disruption of sensorimotor gating in mice and increases the startle response. MK-801 at 0. 50 mg/kg can be used as the appropriate dose for the deficient sensorimotor gating of schizophrenia model in mice.