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在小鼠背侧海马微量注射氯苯那敏可逆转L-组氨酸的抗焦虑样作用并损害情绪记忆。

Dorsal hippocampal microinjection of chlorpheniramine reverses the anxiolytic-like effects of l-histidine and impairs emotional memory in mice.

作者信息

Canto-de-Souza L, Garção D C, Romaguera F, Mattioli R

机构信息

Laboratório de Neurociências, Universidade Federal de São Carlos, Brazil; Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, 14040-901, Ribeirão Preto, Brazil.

Universidade Tiradentes, Rua Lagarto, 264, 49010-390 Aracaju, Brazil.

出版信息

Neurosci Lett. 2015 Feb 5;587:11-6. doi: 10.1016/j.neulet.2014.12.020. Epub 2014 Dec 15.

DOI:10.1016/j.neulet.2014.12.020
PMID:25524405
Abstract

Several findings have pointed to the role of histaminergic neurotransmission in the modulation of anxiety-like behaviors and emotional memory. The elevated plus-maze (EPM) test has been widely used to investigate the process of anxiety and also has been used to investigate the process of learning and memory. Visual cues are relevant to the formation of spatial maps, and as the hippocampus is involved in this task, experiment 1 explored this issue. Experiment 2 investigated the effects of intraperitoneal (i.p.) injections of l-histidine (LH, a precursor of histamine) and of intra-dorsal hippocampus (intra-DH) injections of chlorpheniramine (CPA, an H1 receptor antagonist) on anxiety and emotional memory in mice re-exposed to the EPM. Mice received saline (SAL) or LH i.p. and SAL or CPA (0.016, 0.052, and 0.16 nmol/0.1 μl) intra-DH prior to Trial 1 (T1) and Trial 2 (T2). No significant changes were observed in the number of enclosed-arm entries (EAE) in T1, an EPM index of general exploratory activity. LH had an anxiolytic-like effect that was reversed by intra-DH injections of CPA. T2 versus T1 analysis revealed that only the lower dose of CPA resulted in impaired emotional memory. Combined injections of LH and CPA revealed that higher doses of CPA impair emotional memory. Taken together, these results suggest that LH and H1 receptors present in the dorsal hippocampus are involved in anxiety-related behaviors and emotional memory in mice submitted to EPM.

摘要

多项研究结果表明组胺能神经传递在调节焦虑样行为和情绪记忆中发挥作用。高架十字迷宫(EPM)试验已被广泛用于研究焦虑过程,也被用于研究学习和记忆过程。视觉线索与空间地图的形成相关,由于海马体参与此任务,实验1探讨了这个问题。实验2研究了腹腔注射L-组氨酸(LH,组胺的前体)和背侧海马内注射氯苯那敏(CPA,一种H1受体拮抗剂)对再次暴露于EPM的小鼠焦虑和情绪记忆的影响。在试验1(T1)和试验2(T2)之前,小鼠腹腔注射生理盐水(SAL)或LH,背侧海马内注射SAL或CPA(0.016、0.052和0.16 nmol/0.1 μl)。在T1中,封闭臂进入次数(EAE)未观察到显著变化,EAE是一般探索活动的EPM指标。LH具有抗焦虑样作用,背侧海马内注射CPA可逆转此作用。T2与T1的分析表明,只有较低剂量的CPA导致情绪记忆受损。LH和CPA联合注射表明,较高剂量的CPA损害情绪记忆。综上所述,这些结果表明,背侧海马中存在的LH和H1受体参与了接受EPM试验的小鼠的焦虑相关行为和情绪记忆。

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