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

精神分裂症患者的工作记忆和认知功能障碍以及与精神刺激相关的精神病与额叶和海马区功能障碍密切相关。这些解剖区域具有神经可塑性和长期潜力(LTP)，这是记忆或学习的独特神经机制。本研究采用5-溴-2‘-脱氧尿嘧啶核苷(BrdU)体内标记技术，研究了行为敏化后大鼠海马神经元的发生，即细胞的增殖和存活。取脑进行免疫组织化学三标记荧光染色，以检测成熟BrdU阳性细胞的表型(星形胶质细胞或神经元)。通过反复给予可卡因或苯环利定来建立致敏作用。行为异常的评定依据是运动能力的定量分析和刻板印象的评分。运动活动采用…1、5、10、14天，精神刺激剂治疗组大鼠的刻板行为得分均显著高于对照组。随着精神刺激剂的注射，苯环利定治疗大鼠的编织和共济失调程度逐渐减轻。分别给予可卡因或苯环利定24小时后，细胞增殖与对照组相比没有变化。与对照组相比，重复使用这些精神刺激剂14天，细胞增殖减少了23%-26%。然而，在反复给予精神刺激剂后1周，细胞增殖抑制恢复到对照水平。重复给药后注射BrdU 4周，新生细胞的细胞分化未见改变。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与某些成瘾症状的发生有关，如认知障碍和行为敏感化的获得。较少

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