尼古丁改善 AF64A 诱导的大鼠 Morris 水迷宫空间记忆缺陷。

Nicotine improves AF64A-induced spatial memory deficits in Morris water maze in rats.

机构信息

Institute of Psychology and Behavioral Neuroscience, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.

出版信息

Neurosci Lett. 2010 Jan 18;469(1):88-92. doi: 10.1016/j.neulet.2009.11.050. Epub 2009 Nov 24.

DOI:10.1016/j.neulet.2009.11.050

PMID:19941937

Abstract

Ethylcholine mustard aziridinium ion (AF64A) is a neurotoxic derivative of choline that produces not only long-term presynaptic cholinergic deficits, but also various memory deficits in rats similar to some characteristics observed in Alzheimer's disease patients. This study investigated whether nicotine (NCT) administration attenuated spatial learning deficits induced by intracerebroventricular AF64A treatment. AF64A (6 nmol/6 microl)-or saline (SAL)-treated rats were trained in Morris water maze task. NCT (0.025-0.25mg/kg) was subcutaneously injected 5 min before the training every day. The results showed that moderate dose (0.10mg/kg) of NCT attenuated AF64A-induced prolongation of escape latency. Furthermore, NCT dose-dependently recovered the AF64A-induced decrease of time spent in the target quadrant in the probe test. These results suggest that NCT improves AF64A-induced spatial memory deficits, and thus it is a potential therapeutic agent for the treatment of memory deficits in dementia.

摘要

乙基氯化氨甲酰胆碱（AF64A）是胆碱的神经毒性衍生物，不仅会导致大鼠长期的突触前胆碱能缺陷，还会产生各种类似于阿尔茨海默病患者的记忆缺陷。本研究探讨了尼古丁（NCT）给药是否能减轻脑室内 AF64A 处理引起的空间学习缺陷。用 AF64A（6 nmol/6 微升）或生理盐水（SAL）处理大鼠，在 Morris 水迷宫任务中进行训练。NCT（0.025-0.25mg/kg）每天在训练前 5 分钟皮下注射。结果表明，中等剂量（0.10mg/kg）的 NCT 可减轻 AF64A 引起的逃避潜伏期延长。此外，NCT 剂量依赖性地恢复了 AF64A 引起的在探测测试中目标象限时间减少。这些结果表明，NCT 改善了 AF64A 引起的空间记忆缺陷，因此它是治疗痴呆症记忆缺陷的潜在治疗药物。