Effect of endogenous histamine in the ventral hippocampus on fear memory deficits induced by scopolamine as evaluated by step-through avoidance response in rats
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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通过逐步回避反应评估腹侧海马内源性组胺对东莨菪碱诱导的恐惧记忆缺陷的影响
DOI：
10.1016/j.physbeh.2006.01.004
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发表时间：
2006-04
影响因子：
2.9
通讯作者：
中科院分区：
文献类型：
--
作者：
本研究采用避暗反应的方法研究了腹侧海马区内源性组胺对东莨菪碱所致大鼠恐惧记忆缺陷的影响。大鼠双侧海马腹侧区注射东莨菪碱(I.H.，2，5μg/Site)对主动回避反应有明显的抑制作用，且呈剂量依赖关系。组胺H3拮抗剂氯苯丙特(5，10μg/Site)可剂量依赖性地显著改善东莨菪碱诱导的小鼠恐惧记忆障碍。其先兆作用可被组胺H3受体激动剂Immepip(10μg/Site)完全拮抗。组胺H1受体拮抗剂吡拉明和H2受体拮抗剂西咪替丁也可抑制氯苯丙匹特的预知效应。此外，腹腔注射氯苯丙匹特可显著增强氯苯丙匹特对东莨菪碱所致的恐惧记忆障碍的预知作用。注射组胺前体组氨酸，但被I.H.显著逆转。注射α-氟甲基组氨酸(FMH，10μg/部位)，这是一种选择性和有效的组氨酸脱羧酶抑制剂。结论：腹侧海马区内源性组胺释放增加可改善东莨菪碱诱导的恐惧记忆障碍，其作用机制主要是通过组胺突触前H3受体和突触后H1、H2受体实现的。
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.
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影响因子：
3.3
作者：
E. O. Alvarez;A. M. Banzan-
通讯作者：
E. O. Alvarez;A. M. Banzan-
影响因子：
3.3
作者：
W. Fischer;H. van der Goot
通讯作者：
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影响因子：
2.7
作者：
Giovannini, MG;Bartolini, L;Blandina, P
通讯作者：
Blandina, P
影响因子：
3.6
作者：
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通讯作者：
Kamei, C
影响因子：
2.7
作者：
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通讯作者：
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