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Amino acid neural transmission and cognitive function in the animal model for drug abuse

药物滥用动物模型中的氨基酸神经传递和认知功能

基本信息

批准号：
15591243
负责人：
SUZUKI Toshihito
金额：
$ 2.18万
依托单位：
JUNTENDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591243/
关键词：
coaine phencyclidine hippocampus neurogenesis sen sitization drug abuse rat

项目摘要

The disturbances of working memory and cognitive function in schizophrenia are as well as psychostimulant-related psychosis closely involved in the dysfuntions of frontal lobe and hippocampus. Those anatomical regions have neuroplasticity and long-term potential (LTP), which are unique neural mechanisms for memory or learning. In the present study, we focused on the hippocampal neurogenesis, i.e., cell proliferation and survival, in the rats following a development of behavioral sensitization Cell proliferation in the hippocampus was assessed using in-vivo labeling with 5-bromo-2'-deoxyuridine (BrdU) in adult rats. Brains were processed for triple-label immunohistofluorescence in order to examine phenotype (astrocyte or neuron) of mature BrdU positive cells. The sensitization was established by repeated administration of cocaine or phencyclidine. Behavioral abnormalities were assessed according to a quantitative analysis of locomotor and a score of stereotypy.The locomotor activities a … More nd mean scores for stereotypies in the psychostimulants-treated groups were increased significantly compared to the control group on days 1, 5, 10, 14. The degrees of weaving and ataxia observed in the phencyclidine-treated rats were gradually decreased with injections of psychostimulants. The cell proliferation was unchanged 24 hr after a single administration of cocaine or phencyclidine, compared to the controls, respectively. Repeated administration of these psychostimulants for 14 days decreased cell proliferation by 23-26 %, compared to the controls. However, the reduction of cell proliferation was returned to the control level 1 week following repeated administration of psychostimulants. At 4 weeks after an injection of BrdU subsequent to repeated administration, cell differentiation of newly formed cells was not altered. These data imply that the regulation of hippocampal cell proliferation by cocaine or phencyclidine may be involved in the development of certain symptoms of addiction, such as cognitive impairment and acquisition of behavioral sensitization. Less

精神分裂症的工作记忆和认知功能障碍与精神兴奋剂相关性精神病一样，都与额叶和海马的功能障碍密切相关。这些解剖区域具有神经可塑性和长时程电位（LTP），这是记忆或学习的独特神经机制。在本研究中，我们集中在海马神经发生，即，在发生行为致敏后的大鼠中的细胞增殖和存活在成年大鼠中，使用5-溴-2 ′-脱氧尿苷（BrdU）的体内标记来评估海马中的细胞增殖。处理脑以进行三标记荧光分析，以检查成熟BrdU阳性细胞的表型（星形胶质细胞或神经元）。通过重复给予可卡因或苯环己哌啶建立致敏作用。行为异常根据运动定量分析和刻板行为评分进行评估。 ...更多信息在第1、5、10、14天，与对照组相比，精神兴奋剂治疗组的刻板印象的平均得分显著增加。在苯环利定治疗的大鼠中观察到的编织和共济失调的程度随着精神兴奋剂的注射而逐渐降低。与对照组相比，可卡因或苯环利定单次给药后24小时细胞增殖无变化。与对照组相比，重复给予这些精神兴奋剂14天可使细胞增殖降低23- 26%。然而，细胞增殖的减少在重复给予精神兴奋剂后1周恢复到对照水平。在重复给药后注射BrdU 4周时，新形成细胞的细胞分化没有改变。这些数据表明，可卡因或苯环利定对海马细胞增殖的调节可能参与成瘾的某些症状的发展，如认知障碍和行为敏化的获得。少