An animal model of emotional blunting in schizophrenia.
An animal model of emotional blunting in schizophrenia.
复制标题
DOI：
10.1371/journal.pone.0001360
复制
发表时间：
2007-12-26
期刊：
影响因子：
3.7
通讯作者：
den Boer JA
中科院分区：
文献类型：
--
作者：
Pietersen CY;Bosker FJ;Doorduin J;Jongsma ME;Postema F;Haas JV;Johnson MP;Koch T;Vladusich T;den Boer JA
精神分裂症通常与情绪迟钝有关--对情绪上突出的刺激做出反应的能力减弱--特别是那些代表负面情绪状态的刺激，如恐惧。这种障碍可能源于杏仁核的功能障碍，杏仁核是大脑中参与恐惧处理的区域。本文描述了一种新的精神分裂症情感迟钝动物模型。这个模型包括通过急性给药氯胺酮来干扰大鼠正常的恐惧处理(经典的条件反射)。在CFOS染色、行为分析和神经化学测定组成的一系列实验中，我们证实氯胺酮干扰了恐惧的行为表达，并干扰了杏仁核和相关脑区的正常恐惧处理。我们进一步表明，非典型抗精神病药物氯氮平，但不是典型的抗精神病药物氟哌啶醇或实验性谷氨酸受体2/3激动剂，抑制氯胺酮的作用，并在神经化学水平上保留杏仁核正常的恐惧处理，尽管观察到与恐惧相关的行为仍因氯胺酮注射而受到抑制。我们的结果表明，情绪迟钝对药物治疗的相对抵抗力可能部分是由于传统疗法无法针对参与情绪处理的多个解剖和功能大脑系统。假设并讨论了一个概念模型，该模型协调了我们在神经化学和行为方面的发现。
Schizophrenia is often associated with emotional blunting—the diminished ability to respond to emotionally salient stimuli—particularly those stimuli representative of negative emotional states, such as fear. This disturbance may stem from dysfunction of the amygdala, a brain region involved in fear processing. The present article describes a novel animal model of emotional blunting in schizophrenia. This model involves interfering with normal fear processing (classical conditioning) in rats by means of acute ketamine administration. We confirm, in a series of experiments comprised of cFos staining, behavioral analysis and neurochemical determinations, that ketamine interferes with the behavioral expression of fear and with normal fear processing in the amygdala and related brain regions. We further show that the atypical antipsychotic drug clozapine, but not the typical antipsychotic haloperidol nor an experimental glutamate receptor 2/3 agonist, inhibits ketamine's effects and retains normal fear processing in the amygdala at a neurochemical level, despite the observation that fear-related behavior is still inhibited due to ketamine administration. Our results suggest that the relative resistance of emotional blunting to drug treatment may be partially due to an inability of conventional therapies to target the multiple anatomical and functional brain systems involved in emotional processing. A conceptual model reconciling our findings in terms of neurochemistry and behavior is postulated and discussed.
登录
查看更多内容
影响因子：
4.5
作者：
Edwards, Jane;Pattison, Philippa E.;Wales, Roger J.
通讯作者：
Wales, Roger J.
影响因子：
10.6
作者：
Castner, SA;Goldman-Rakic, PS
通讯作者：
Goldman-Rakic, PS
DOI：
10.3758/bf03211975
发表时间：
1976-01-01
期刊：
ANIMAL LEARNING & BEHAVIOR
影响因子：
--
作者：
BOLLES, RC;COLLIER, AC
通讯作者：
COLLIER, AC
影响因子：
1.9
作者：
Greba, Q;Kokkinidis, L
通讯作者：
Kokkinidis, L
影响因子：
56.9
作者：
Frankland, PW;Bontempi, B;Silva, AJ
通讯作者：
Silva, AJ