Cassel J C, Kelche C
Département de Neurophysiologie, Centre de Neurochimie du CNRS INSERM U.44, Strasbourg.
Physiol Behav. 1989 Sep;46(3):347-53. doi: 10.1016/0031-9384(89)90002-4.
Long-Evans female rats were "trained" in an 8-arm radial maze and subsequently tested under systemic treatment with physostigmine (0.05 mg/kg, IP), scopolamine methylbromide (MBr) and scopolamine hydrobromide (HBr; 0.5 mg/kg, IP), whose effects were compared to those of aspirative lesions of the fimbria-fornix pathways. During the predrug trials, rats with lesions showed impaired performances compared to those of intact rats. Whereas physostigmine had no significant effect in either group, scopolamine HBr impaired performances of intact rats in a manner closely parallel to all measured behavioral effects of the lesions (errors, "correct arms" and strategies). The scopolamine HBr-induced deficits were not correlated with the percentage of "spatial" strategies. Under scopolamine HBr treatment the performances of rats showing preferences for "spatial" strategies did not differ significantly from those of rats showing preferences for "orientation" strategies. These results provide further support for the involvement of cholinergic processes in working memory and suggest that scopolamine-induced central cholinergic disruption may mimic the effects of fimbria-fornix lesions in an 8-arm radial maze. They also somewhat qualify previous reports on 1) the poor sensitivity of an uninterrupted radial maze testing procedure to pharmacological treatment and 2) the abilities of rats to resist muscarinic blockade depending on the strategies they use in the maze.
将长 Evans 雌性大鼠置于八臂放射状迷宫中进行“训练”,随后在系统给予毒扁豆碱(0.05 毫克/千克,腹腔注射)、甲溴东莨菪碱和氢溴酸东莨菪碱(0.5 毫克/千克,腹腔注射)的情况下进行测试,并将这些药物的效果与穹窿海马伞通路抽吸性损伤的效果进行比较。在给药前的试验中,与完整大鼠相比,损伤大鼠的表现受损。毒扁豆碱对两组均无显著影响,而氢溴酸东莨菪碱以与损伤的所有行为学效应(错误、“正确臂”和策略)密切平行的方式损害了完整大鼠的表现。氢溴酸东莨菪碱诱导的缺陷与“空间”策略的百分比无关。在氢溴酸东莨菪碱治疗下,表现出对“空间”策略偏好的大鼠的表现与表现出对“定向”策略偏好的大鼠的表现没有显著差异。这些结果为胆碱能过程参与工作记忆提供了进一步支持,并表明东莨菪碱诱导的中枢胆碱能破坏可能在八臂放射状迷宫中模拟穹窿海马伞损伤的效应。它们也在一定程度上修正了先前关于 1)连续放射状迷宫测试程序对药物治疗敏感性较差以及 2)大鼠根据其在迷宫中使用的策略抵抗毒蕈碱阻断能力的报道。