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

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精神病密切相关，与额叶和海马功能障碍密切相关。这些解剖区域具有神经可塑性和长期电位（LTP），这是记忆或学习的独特神经机制。在本研究中，我们重点研究了行为致敏后大鼠海马神经发生，即细胞增殖和存活，使用5-溴-2'-脱氧尿苷（BrdU）在体内标记法评估成年大鼠海马细胞增殖。为了检测成熟BrdU阳性细胞的表型（星形胶质细胞或神经元），对脑进行三标记免疫组织荧光处理。通过反复给药可卡因或苯环利定建立致敏作用。通过定量分析运动能力和刻板印象评分来评估行为异常。在第1天、第5天、第10天、第14天，精神兴奋剂治疗组的刻板印象得分和平均得分均显著高于对照组。注射精神兴奋剂后，苯环利定治疗大鼠的织织程度和共济失调程度逐渐降低。与对照组相比，单次给药可卡因或苯环利定24小时后细胞增殖没有变化。与对照组相比，连续14天反复使用这些精神兴奋剂可使细胞增殖减少23- 26%。然而，在重复使用精神兴奋剂1周后，细胞增殖的减少恢复到对照水平。在重复给药后注射BrdU 4周，新形成细胞的细胞分化未发生改变。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涉及某些成瘾症状的发展，如认知障碍和行为敏感化的获得。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