[Significance of the pharmacotherapy of schizophrenia in the emotional context processing of cognition].

Ken Inada, Hidehiro Oshibuchi, Jun Shigooka
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Abstract

Emotional disorders and cognitive dysfunctions are important treatment targets in psychiatric clinical settings. The biological mechanisms of emotional disorders have been studied with methods that include fear conditioning, schizophrenia models are studied with methamphetamine-induced reverse tolerance in rats, and dynamic changes in brain neurotransmitters are studied with microdialysis and high-performance liquid chromatography. We combined these methods in order to evaluate dopamine dynamics in the amygdala and the biological bases and relationships of emotional disorder and cognitive dysfunction. Fear-conditioned rats showed freezing behavior and dopamine release in the amygdala in response to conditioned stimuli. Methamphetamine-induced reverse tolerance rats showed increased dopamine release in the amygdala in response to conditioned stimuli. The increased release of dopamine continued after the freezing behavior had ended. This increased and long-lasting dopamine release may reflect abnormal emotional context processing in cognition in schizophrenia. Antipsychotic drugs, such as haloperidol, aripiprazole, and clozapine, suppress this increased release of dopamine in the amygdala in response to conditioned stimuli. These findings suggest that antipsychotic drugs may stabilize abnormal emotional context processing in cognition in this model. We conclude that the significance of pharmacotherapy in schizophrenia is that antipsychotic drugs stabilize the emotional context processing in cognition and adjust the relationship of emotion and cognition.

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精神分裂症药物治疗在认知情绪情境加工中的意义
情绪障碍和认知功能障碍是精神病学临床设置的重要治疗目标。利用恐惧条件反射等方法研究了情绪障碍的生物学机制,利用甲基苯丙胺诱导的大鼠反向耐受性研究了精神分裂症模型,并利用微透析和高效液相色谱法研究了脑神经递质的动态变化。我们将这些方法结合起来,以评估杏仁核中的多巴胺动态以及情绪障碍和认知功能障碍的生物学基础和关系。恐惧条件下的大鼠在条件刺激下表现出冻结行为和杏仁核释放多巴胺。甲基苯丙胺诱导的反向耐受大鼠在条件刺激下杏仁核多巴胺释放增加。在冻结行为结束后,多巴胺的释放继续增加。这种增加且持续的多巴胺释放可能反映了精神分裂症患者认知中异常的情绪背景处理。抗精神病药物,如氟哌啶醇、阿立哌唑和氯氮平,抑制杏仁核对条件刺激的多巴胺释放增加。这些发现表明抗精神病药物可能稳定了该模型中认知中异常的情绪背景加工。我们认为,精神分裂症药物治疗的意义在于,抗精神病药物稳定了认知中的情绪情境加工,调节了情绪与认知的关系。
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