Propofol facilitates the development of long-term depression (LTD) and impairs the maintenance of long-term potentiation (LTP) in the CA1 region of the hippocampus of anesthetized rats

Memory is sensitive to the short-acting anesthetic (2,6-diisopropylphenol) propofol, but the underlying mechanism is little known. Here, we have examined the effects of propofol on synaptic plasticity in the CA1 region of the hippocampus of anesthetized rats. We found that low dose of propofol (20 mg/kg, i.p.) did not affect the basal transmission, but enhanced prominently the development of long-term depression (LTD) and impaired the maintenance of long-term potentiation (LTP). The impairment of LTP maintenance and enhancement of LTD development may contribute to propofol-induced deficits in memory following propofol anesthesia. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

γ-氨基丁酸受体和甘氨酸受体在大鼠丙泊酚麻醉中的作用

目的 研究丙泊酚对大鼠海马CA1区电刺激诱发兴奋性突触后电流(EPSC)的影响,分析γ-氨基丁酸(GABA)受体和甘氨酸受体在丙泊酚麻醉中的作用.方法 断头法分离wistar大鼠(13～19 d)海马半脑,切出400 μm厚度的海马脑片,全细胞膜片钳技术记录CA1区锥体神经元EPSC.80张脑片分为八组:脂肪乳剂组,50 μmol/L丙泊酚组,100 μmol/L丙泊酚组,200 μmol/L丙泊酚组,SR95531组,士的宁组,SR95531+100 μmol/L丙泊酚组,士的宁+100 μmol/L丙泊酚组,每组10张.SR95531+100 μmol/L丙泊酚组和士的宁+100 μmol/L丙泊酚组先在循环液中加入10 μmol/L SR95531或4 μmol/L士的宁预孵脑片30 min.八组均记录基础EPSC 10 min,然后加入不同药物,继续记录EPSC 40 min.膜钳制电压为-70 mV.结果 脂肪乳剂、SR95531和士的宁对EP-SC幅值无影响;丙泊酚呈剂量依赖性的抑制EPSC幅值,50、100、200 μmol/L丙泊酚最大抑制EPSC幅值为14.4%、52.3%、67.8%;SR95531+100 μmol/L丙泊酚组加入丙泊酚后,EPSC幅值基本无改变;士的宁+100 μmol/L丙泊酚组加入丙泊酚后,EPSC幅值仍然下降,最大抑制程度为34.7%.结论 丙泊酚主要通过增强GABAA受体功能使兴奋性突触活动降低,甘氨酸受体在其中起到协同和调节作用.