Dose-related impairment of spatial learning by intrahippocampal scopolamine: Antagonism by ondansetron, a 5-HT3 receptor antagonist
Dose-related impairment of spatial learning by intrahippocampal scopolamine: Antagonism by ondansetron, a 5-HT3 receptor antagonist
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DOI：
10.1016/s0166-4328(97)80988-6
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发表时间：
1997-01-01
影响因子：
2.7
通讯作者：
Samanin, R
中科院分区：
文献类型：
--
作者：
Carli, M;Luschi, R;Samanin, R
为了研究海马毒蕈碱受体在空间学习中的作用，将不同剂量的东莨菪碱双侧注射到接受双平台空间辨别任务训练的大鼠背侧海马的 CAI 区域。每次训练前 10 分钟服用东莨菪碱，剂量范围为 3.75 至 15 μg/ul，会损害选择准确性，对选择潜伏期没有影响，仅在训练第 1 天服用 7.5 μg 以及在训练第 1 天和第 2 天服用 15 μg 时会增加遗漏错误。没有剂量影响非空间视觉辨别任务的选择准确性或延迟。每次训练前30分钟皮下注射1μg/kg昂丹司琼（一种5-HT3受体拮抗剂）可防止海马内3.75μg东莨菪碱对选择准确性的损害，但0.1μg/kg昂丹司琼没有这种作用。昂丹司琼本身的剂量不会改变空间学习的获得。结果表明，背侧海马中相对较低剂量的东莨菪碱会选择性地损害空间辨别任务的获得，而阻断 5-HT3 受体可以防止毒蕈碱拮抗剂引起的缺陷。讨论了海马内东莨菪碱引起的空间学习缺陷在模拟阿尔茨海默氏病记忆障碍的某些方面的效用。
To study the role of hippocampal muscarinic receptors in spatial learning, various doses of scopolamine were injected bilaterally into the CAI region of the dorsal hippocampus of rats trained in a two-platform spatial discrimination task. Scopolamine administered 10 min before each training session at doses ranging from 3.75 to 15 mu g/ul impaired choice accuracy, had no effect on choice latency and increased the errors of omission only with 7.5 mu g on day 1 and with 15 mu g on days 1 and 2 of training. No dose affected choice accuracy or latency of a non-spatial visual discrimination task. A subcutaneous dose of 1 mu g/kg ondansetron, a 5-HT3 receptor antagonist, 30 min before each training session prevented the impairment of choice accuracy by intrahippocampal 3.75 mu g scopolamine but 0.1 mu g/kg ondansetron had no such effect. No dose of ondansetron by itself modified the acquisition of spatial learning. The results suggest that relatively low doses of scopolamine in the dorsal hippocampus selectively impair the acquisition of a spatial discrimination task, and that blockade of 5-HT3 receptors prevents the deficit caused by the muscarinic antagonist. The utility of the deficit of spatial learning induced by intrahippocampal scopolamine for modelling some aspects of memory disturbances in Alzheimer's disease is discussed.