ANIMAL MODELS OF NEUROPSYCHIATRIC DISORDERS

神经精神疾病的动物模型

• 批准号: 3921936
• 负责人: J N CRAWLEY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3921936
• 关键词: amphetamines; apomorphine; benzodiazepine receptor; benzodiazepines; brain metabolism; caudate nucleus; cholecystokinin; disease /disorder model; haloperidol; hypothalamus; laboratory rat; mental disorders; microinjections; model design /development; nervous system disorder; neurochemistry; neuropharmacology; neurotensin; neurotransmitter metabolism; nucleus accumbens; psychopharmacology; schizophrenia

The microdialysis technique, for continuous in vivo sampling of extracellular fluid in anatomically specific brain sites, was established in our laboratory this year. Peripheral administration of haloperidol increased concentrations of DOPAC and HVA in the caudate nucleus, while peripheral administration of amphetamine decreased DOPAC and HVA in the nucleus accumbens as previously described, validating our methodology. Microinjection of nanomole quantities of cholecystokinin and of neurotension into the ventral tegmentum of rats was shown to increase DOPAC and HVA in the nucleus accumbens, for up to 2 hours. Intraventricular injection of antiserum from patients with Sydenham's Chorea produced a small, highly variable increase in DOPAC and HVA in the caudate nucleus of rats. Peripheral administration of alprazolam caused a potentiation of the effects of haloperidol on increasing DOPAC and HVA in the caudate nucleus and in the prefrontal cortex of the rat. Microinjection of apomorphine into the prefrontal cortex produced a significant decrease in DOPAC and HVA in the caudate nucleus of rats. Microdialysis in the awake, freely moving rat revealed a small increase in DOPAC and HVA in the nucleus accumbens during periods of hyperlocomotion in rats placed in a Digiscan activity monitor, as compared to periods of rest in a holding cage. The microdialysis technique appears to be useful for addressing many of the anatomical, biochemical, and behavioral hypotheses of dopaminergic mechanisms relevant to the etiology and treatment of schizophrenia.

微透析技术，用于连续体内取样， 在解剖学上特定的脑部位的细胞外液， 今年在我们实验室成立。 外周施用 氟哌啶醇增加DOPAC和HVA的浓度， 尾状核，而外周给药安非他明 减少多巴胺和HVA在脑桥核如前所述 描述，验证我们的方法。 纳摩尔显微注射 大量的胆囊收缩素和神经紧张素进入腹侧 大鼠的被盖被证明增加DOPAC和HVA在 去核2小时。 脑室注射 西德纳姆舞蹈病患者的抗血清产生了一个小的， 尾状核中DOPAC和HVA的高度可变增加 老鼠。 阿普唑仑的外周给药引起了 氟哌啶醇增加DOPAC和 大鼠尾状核和前额叶皮层的HVA。 将阿扑吗啡微量注射到前额叶皮层， 尾状核中DOPAC和HVA的显著降低， 大鼠 在清醒的自由活动的大鼠中进行微透析， 在Dopac和HVA的小增加，在脑桥核， 置于Digiscan活动中的大鼠的过度运动期 监视器，与在保持笼中的休息时间相比。 的 微透析技术似乎对解决许多问题是有用的。 解剖学、生物化学和行为学的假设， 多巴胺能机制的病因和治疗 精神分裂症