酒精对大鼠背侧纹状体长时程突触抑制的影响

Effect of Alcohol on the Induction of Long-term Depression in the Dorsal Striatum in Rats

目的:建立大鼠背侧纹状体长时程突触抑制(LTD)的诱导方法,并观察60 mmol/L酒精对大鼠背侧纹状体LTD诱导的影响,初步探讨酒精的作用机制。方法:制备纹状体冠状切面脑片,双极钨丝电极刺激皮层-纹状体传入通路,在大鼠背侧纹状体部位记录诱发的群峰电位(population spike,PS)。预先灌流60 mmol/L酒精及N-甲基-D-天冬氨酸(NMDA)受体阻断剂MK-801,再给予强直刺激。结果:对照组给予强直刺激后诱导出明显的LTD,PS幅值减小到原先的20％左右,并持续60 min以上;灌流酒精10 min再给予强直刺激,PS幅值出现先减小而后增加的变化,60 min时已经恢复到强直刺激前的80％;灌流MK-801后给予强直刺激阻断LTD的诱导。结论:强直刺激皮层-纹状体兴奋性传入通路可在背侧纹状体诱导明显的LTD,灌流酒精不影响LTD的产生,然而会影响LTD的保持,NMDA受体参与纹状体LTD的诱导。

Objective:To establish the method of the induction of long-term depression (LTD) in the dorsalstriatum of rats and to investigate the effect of alcohol on the synaptic plasticity in striatum. Methods: Coronary brain slices including striatum were prepared, a bipolar tungsten electrode was used to stimulate the cortex-striatum pathway and population spike (PS) in the dorsalstriatum area was recorded. Alcohol (60 mmol/L) and NMDA receptor antagonist MK-801 were pretreated before the delivery of high frequency stimulation (HFS) to investigate the mechanism of the effect of alcohol on the synaptic plasticity in the striatum. Results:In control slice,a significant LTD was found after HFS, and the PS amplitude was reduced to 20% of the value that showed before HFS and persisted at least 60 min. When the slice was pretreated with alcohol (60 mmol/L) 10 min before HFS there was still a reduction of the PS amplitude but it was recovered slowly to 80% of the control value in about an hour. Pretreatment of slice with MK-801 blocked the induction of LTD. Conclusion: NMDA receptor may play a key role in the induction of LTD in the striatum. Alcohol can not block LTD in the striatum but it will shorten the period of LTD induced by HFS.