Neuroplasticity, memory and drug-induced reinforcement in histamine H1-receptor- and histidine-decarboxylase knockout mice

组胺 H1 受体和组氨酸脱羧酶敲除小鼠的神经可塑性、记忆力和药物诱导的强化

• 批准号: 24390832
• 负责人: Professor Dr. Ekrem Dere
• 金额: --
• 依托单位: Forschungs- und Behandlungszentrum FBZ
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/24390832?language=en
• 关键词: Neuroplasticity; memory; drug; induced; reinforcement

The role of neuronal histamine in learning and memory, neuroplasticity as well as drug-induced place preference will be studied using knockouts (KO) of the H1-receptor (H1-R) and the enzyme histidine-decarboxylase (HDC), which converts the precursor histidine to histamine. The HDC- and H1-R-KO mice will be evaluated in terms of delay-dependent object recognition, object-place memory, and temporal order memory. Histamine has been implicated in synaptic plasticity. Synaptic long-term potentiation- and depression will be measured in brain regions relevant to these different types of object memory (e.g., hippocampus, medial prefrontal -and perirhinal cortex). Since deficient episodic memory is the cardinal cognitive symptom in Alzheimer¿s disease, and since it¿s pathology also includes degeneration of histaminergic neurons, HDC- and H1-R-KO mice are to be tested in an episodic-like memory task. The brain s histamine system exerts inhibitory effects on the brain¿s reinforcement systems by an antagonistic action on the mesolimbic dopamine system. The H1-R- and HDC-KO mice will be examined for both morphine- and cocaine-induced place preference. By means of in-vivo microdialysis the effects of a behaviorally active dose of cocaine on extracellular dopamine levels in the neostriatum of freely moving HDC-C57BL/6-KO and wild type mice will be determined. HDC-KO mice will also be subjected to a morphometrical analysis of the mesolimbic dopamine system.

神经元组胺在学习和记忆、神经可塑性以及药物诱导的位置偏好中的作用将通过敲除（KO）H1受体（H1-R）和将前体组胺转化为组胺的酶组胺脱羧酶（HDC）来研究。将在延迟依赖性物体识别、物体位置记忆和时序记忆方面评价HDC-和H1-R-KO小鼠。组胺与突触可塑性有关。突触长时程增强和抑郁将在与这些不同类型的物体记忆相关的大脑区域中测量（例如，海马体、内侧前额叶皮层和嗅周皮层）。由于缺乏情景记忆是阿尔茨海默病的主要认知症状，并且由于其病理学还包括组胺能神经元的变性，因此将在情景样记忆任务中测试HDC-和H1-R-KO小鼠。大脑的组胺系统通过对中脑边缘多巴胺系统的拮抗作用对大脑的强化系统产生抑制作用。将检查H1-R-和HDC-KO小鼠的吗啡和可卡因诱导的位置偏爱。通过体内微透析，将确定行为活性剂量的可卡因对自由移动的HDC-C57 BL/6-KO和野生型小鼠的新纹状体中细胞外多巴胺水平的影响。还将对HDC-KO小鼠进行中脑边缘多巴胺系统的形态测定分析。