Shear D A, Dong J, Haik-Creguer K L, Bazzett T J, Albin R L, Dunbar G L
Brain Research Laboratory, Department of Psychology, Central Michigan University, Mt. Pleasant, Michigan 48859, USA.
Exp Neurol. 1998 Apr;150(2):305-11. doi: 10.1006/exnr.1998.6767.
Chronic intrastriatal administration of quinolinic acid (QA) in the rat produces a pattern of neurodegeneration similar to that seen in Huntington's disease (HD). Although these changes have been related to transient motor abnormalities, the effects of chronic QA administration on cognitive abilities have not been assessed. The present study investigated whether the striatal deterioration observed during chronic QA administration produces cognitive impairments in this animal model of HD by testing the effects of chronic administration of QA on spatial learning ability of rats in a radial arm water maze (RAWM) task. Rats were given bilateral implantation of a chronic dialysis probe apparatus which delivered either vehicle or QA (20 mM) into the striatum. Beginning 1 day after implantation, the rats were tested daily for 3 weeks in the RAWM. Nocturnal activity levels were also assessed at 1-, 3-, 5-, 7-, 14-, and 21-days following probe implantation. Results of behavioral testing indicated that chronic exposure to QA causes spatial learning deficits in the RAWM task with only a transient increase in activity levels. Collectively, these results suggest that chronic striatal exposure to QA mimics some aspects of the cognitive deficits observed in HD.
在大鼠纹状体内长期注射喹啉酸（QA）会产生一种类似于亨廷顿舞蹈病（HD）的神经退行性变模式。尽管这些变化与短暂的运动异常有关，但长期注射QA对认知能力的影响尚未得到评估。本研究通过测试长期注射QA对大鼠在放射状臂水迷宫（RAWM）任务中空间学习能力的影响，来探究在这种HD动物模型中，长期注射QA期间观察到的纹状体退化是否会导致认知障碍。给大鼠双侧植入慢性透析探针装置，该装置将溶剂或QA（20 mM）输送到纹状体中。从植入后第1天开始，大鼠在RAWM中每天接受测试，持续3周。在探针植入后的第１天、第３天、第５天、第７天、第14天和第21天，还评估了夜间活动水平。行为测试结果表明，长期暴露于QA会导致在RAWM任务中出现空间学习缺陷，且活动水平仅短暂增加。总体而言，这些结果表明，长期纹状体暴露于QA模拟了HD中观察到的认知缺陷的某些方面。
