Locchi Federica, Dall'Olio Rossella, Gandolfi Ottavio, Rimondini Roberto
Department of Pharmacology, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
Neurosci Lett. 2007 Jul 18;422(3):213-6. doi: 10.1016/j.neulet.2007.06.023. Epub 2007 Jun 17.
The present study was performed to validate a spatial working memory task using pharmacological manipulations. The water escape T-maze combines the advantages of the Morris water maze and the T-maze while minimizing the disadvantages. Scopolamine (1mg/kg), a drug that affects cognitive function in spatial working memory tasks, significantly decreased the rats' performance in the present delayed alternation task. Glutamate neurotransmission plays an important role in the maintenance of working memory; rats treated with dizocilpine (MK-801; 0.125-0.25mg/kg), a N-methyl-d-aspartate (NMDA) receptor antagonist, were impaired in this task. In agreement with evidence showing a functional interaction between ionotropic and metabotropic glutamatergic receptors, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a mGlu(5) receptor antagonist, at a dose (1mg/kg) which by itself had no significant effects, enhanced MK-801-induced impairments of spatial working memory. These evidences suggest that the water escape T-maze might be a valid method to assess spatial working memory, sensitive to pharmacological manipulations.
本研究旨在通过药理学操作验证一种空间工作记忆任务。水迷宫T型迷宫结合了Morris水迷宫和T型迷宫的优点,同时将缺点降至最低。东莨菪碱(1mg/kg)是一种影响空间工作记忆任务中认知功能的药物,在当前的延迟交替任务中显著降低了大鼠的表现。谷氨酸神经传递在工作记忆的维持中起重要作用;用N-甲基-D-天冬氨酸(NMDA)受体拮抗剂地佐环平(MK-801;0.125-0.25mg/kg)处理的大鼠在该任务中受损。与显示离子型和代谢型谷氨酸能受体之间存在功能相互作用的证据一致,mGlu(5)受体拮抗剂2-甲基-6-(苯乙炔基)-吡啶(MPEP)在剂量为1mg/kg时本身无显著影响,但增强了MK-801诱导的空间工作记忆损伤。这些证据表明,水迷宫T型迷宫可能是评估空间工作记忆的有效方法,对药理学操作敏感。