Effect of endogenous histamine in the ventral hippocampus on fear memory deficits induced by scopolamine as evaluated by step-through avoidance response in rats

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• 作者：Chaoyang Yu ; Yao Shen ; Lisha Xu ; Yuanyuan Zhu ; Zhenbin Zhuge ; Yuwen Huang ; Timmerman Henk ; Leurs Rob ; Erqing Wei and Zhong Chen
• 关键词：Clobenpropit ; Active avoidance response ; Scopolamine ; Fear memory ; α ; -Fluoromethylhistidine ; Histamine
• 刊名：Physiology and Behavior
• 出版年：2006
• 出版时间：15 April 2006
• 年：2006
• 卷：87
• 期：4
• 页码：687-693
• 全文大小：248 K

文摘

In the present study, the effects of endogenous histamine in the ventral hippocampus on fear memory deficits induced by scopolamine were investigated as evaluated by step-through avoidance response in adult male rats. Bilateral ventral hippocampal injection of scopolamine (i.h., 2, 5 μg/site) significantly produced depressant effects on the active avoidance response in a dose-dependent manner. Histamine H₃-antagonist clobenpropit (5, 10 μg/site) significantly ameliorated the fear memory deficits induced by scopolamine in a dose-dependent manner. Its procognitive effect was completely antagonized by immepip (10 μg/site), a selective histamine H₃-agonist. Both histamine H₁-antagonist pyrilamine and H₂-antagonist cimetidine, also inhibited the procognitive effects of clobenpropit. Additionally, the procognitive effects of clobenpropit on the fear memory deficits induced by scopolamine were significantly potentiated by intraperitoneal (i.p.) injection of histidine, a precursor of histamine, but markedly reversed by i.h. injection of α-fluoromethylhistidine (FMH, 10 μg/site), a selective and potent histidine decarboxylase inhibitor. It is concluded that the increased endogenous histamine release in the ventral hippocampus ameliorates the scopolamine-induced fear memory deficits, and its action is mainly mediated by histamine presynaptic H₃-receptors and postsynaptic H₁- and H₂-receptors.