Effects of chronic scopolamine administration on spatial working memory and hippocampal receptors related to learning
Effects of chronic scopolamine administration on spatial working memory and hippocampal receptors related to learning
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DOI：
10.1097/fbp.0b013e32835a38af
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发表时间：
2012-12-01
影响因子：
1.6
通讯作者：
Sonmez, Yonca
中科院分区：
文献类型：
--
作者：
Doguc, Duygu K.;Delibas, Namik;Sonmez, Yonca
东莨菪碱已被用作神经精神药理学的标准药物，可导致与健康人类和动物衰老过程中出现的认知缺陷相似的症状。已知东莨菪碱是一种非选择性毒蕈碱受体阻滞剂，但其对某些海马受体表达的慢性影响尚不清楚。本研究的目的是确定长期服用东莨菪碱对两种不同学习任务（水迷宫和八臂径向迷宫）中海马受体表达和空间工作记忆的影响。雄性大鼠（8-12 个月）接受了这两项任务的训练。随后，不同组分别给予生理盐水或0.1、0.8或2 mg/kg氢溴酸东莨菪碱，持续15天。给药后，对大鼠重新测试这两项任务，并通过蛋白质印迹分析评估海马 NR2A、NR2B、nAChR α 7 和 mAChRM1 受体的表达。在这两项任务中，与对照组相比，所有组的空间工作记忆均呈剂量依赖性下降。在受体表达方面，0.8和2 mg/kg东莨菪碱给药显着降低NR2A蛋白表达，这证实了海马胆碱能受体和谷氨酸能受体之间相互作用的建议。行为药理学 23：762-770 (C) 2012 Wolters Kluwer Health 垂直条 Lippincott Williams & Wilkins。
Scopolamine has been used in neuropsychopharmacology as a standard drug that leads to symptoms mimicking cognitive deficits seen during the aging process in healthy humans and animals. Scopolamine is known to be a nonselective muscarinic receptor blocker, but its chronic effect on the expression of certain hippocampal receptors is not clear. The aim of the present study was to determine the effect of chronic scopolamine administration on hippocampal receptor expression and spatial working memory in two different learning tasks, the water maze and the eight-arm radial maze. Male rats (8-12 months) were trained in both tasks. Subsequently, different groups received physiological saline or 0.1, 0.8, or 2 mg/kg scopolamine hydrobromide, respectively, for 15 days. After drug administration, the rats were retested for both tasks, and hippocampal expressions of NR2A, NR2B, nAChR alpha 7, and mAChRM1 receptors were assessed by western blotting analysis. In both tasks, the spatial working memory was decreased dose dependently in all groups compared with the control group. In terms of receptor expressions, 0.8 and 2 mg/kg scopolamine administration significantly decreased NR2A protein expression, which corroborates suggestions of an interaction between cholinergic and glutamatergic receptors in the hippocampus. Behavioural Pharmacology 23: 762-770 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.