Cells in midline thalamus, central amygdala, and nucleus accumbens responding specifically to antipsychotic drugs
Cells in midline thalamus, central amygdala, and nucleus accumbens responding specifically to antipsychotic drugs
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DOI：
10.1007/s00213-003-1423-0
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发表时间：
2003-06-01
影响因子：
3.4
通讯作者：
Lange, N
中科院分区：
文献类型：
--
作者：
Cohen, BM;Cherkerzian, S;Lange, N
原理：确定不同类型的抗精神病药物产生相似效果的脑区，特别是这些效果与缺乏抗精神病疗效的药物所没有的共同效果，为抗精神病药物的临床效果如何以及在何处介导提供了证据。
目的：在本研究中，比较了给予典型抗精神病药氟哌啶醇、抗精神病药氯氮平和非典型抗精神病药奥氮平，以及镇静药苯海拉明和抗焦虑药劳拉西泮后，细胞激活标志物Fos蛋白的表达模式。
方法：动物（斯普拉格 - 道利大鼠，每组3只）接受腹腔注射氟哌啶醇（1mg/kg）、氯氮平（20mg/kg）、奥氮平（5mg/kg）、盐酸苯海拉明（1mg/kg）、劳拉西泮（5mg/kg）或赋形剂（2%乳酸，1ml/kg）。给药2小时后，处死动物。通过对先前认为对所有抗精神病药物有反应的区域（包括伏隔核、中央杏仁核和中央内侧丘脑）进行Fos样抗体的免疫组织化学观察激活细胞的模式。用半自动方法对Fos染色的细胞进行计数。
结果：给予每种抗精神病药物后，伏隔核、中央杏仁核和中央内侧丘脑的Fos阳性细胞模式和数量非常相似。给予抗精神病药物后，明显激活的细胞数量比给予赋形剂后多得多，每种药物与赋形剂在每个区域的差异具有高度统计学意义。劳拉西泮在中央杏仁核产生的细胞明显激活在程度和位置上与抗精神病药物相似，但分布不完全相同。苯海拉明在任何测试部位均未产生细胞明显激活。
结论：典型和非典型抗精神病药物在伏隔核、中央内侧丘脑和中央杏仁核中具有独特的强烈细胞激活模式。抗精神病药物诱导的杏仁核激活与劳拉西泮有共同之处，但抗精神病药物引起的丘脑和伏隔核激活比劳拉西泮强得多。激活细胞的模式可能与抗精神病药物的治疗作用有关。
Rationale: Determining brain regions in which neuroleptic drugs of different types produce similar effects, especially where these effects are not shared with drugs lacking antipsychotic efficacy, provides evidence as to how and where the clinical effects of neuroleptic drugs are mediated. Objective: For this study, the pattern of expression of the protein Fos, a marker of cellular activation, was compared after administration of the typical neuroleptic haloperidol, the antipsychotic drug clozapine, and the atypical neuroleptic olanzapine, as well as the sedative drug diphenhydramine and the anxiolytic lorazepam. Methods: Animals (Sprague-Dawley rats, three per cohort) received intraperitoneal injections of haloperidol (1 mg/kg), clozapine (20 mg/kg), olanzapine (5 mg/kg), diphenhydramine hydrochloride (1 mg/kg), lorazepam (5 mg/kg) or vehicle (2% lactic acid, 1 ml/kg). Two hours after drug administration, animals were killed. Patterns of activated cells were observed by immunohistochemistry for Fos-like antibodies in regions previously suggested as responding to all antipsychotic drugs, including nucleus accumbens, central amygdala, and central medial thalamus. Cells staining for Fos were counted by semi-automated methods. Results: A very similar pattern and number of Fos positive cells in nucleus accumbens, central amygdala, and central medial thalamus followed administration of each antipsychotic drug. The numbers of apparently activated cells were much greater following antipsychotic drug administration than after vehicle, with differences between each drug and vehicle being highly statistically significant in each region. Lorazepam produced apparent activation of cells of the central amygdala similar in degree and location but not identical in distribution to that of antipsychotic drugs. Diphenhydramine produced no apparent activation of cells in any of the sites tested. Conclusion: Typical and atypical antipsychotic drugs shared a distinctive pattern of robust activation of cells in nucleus accumbens, central medial thalamus, and central amygdala. Antipsychotic drug-induced activation of amygdala was shared by lorazepam, but activation of thalamus, and nucleus accumbens was much greater following antipsychotic drugs than following lorazepam. The pattern of activated cells may be relevant to the therapeutic actions of antipsychotic drugs.