Pharmacological effect of Clozapine on emotional disfunction in a rat model of vulnerability to stress

氯氮平对应激大鼠模型情绪障碍的药理作用

• 批准号: 19591376
• 负责人: ISHIGOOKA Jun
• 金额: $ 2.08万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19591376/
• 关键词: 恐怖条件づけ; ドパミン; マイクロダイアリシス; 抗精神病薬; クロザピン; 統合失調症; 扁桃体; 覚せい剤過感受性; 脆弱性; 恐怖条件付け; 脳内微小透析法

Aripiprazole and haloperidol equally suppressed the marked increase in extracellular dopamine levels in fear-conditioned rats, whereas haloperidol increased and aripiprazole decreased basal dopamine levels. The effect of antipsychotics would attenuate the dopamine fear response in the amygdala, modulating basal dopamine level.Both of haloperidol and clozapine significantly increased the basal dopamine level in the basolateral nucleus of amygdala in a dose-related fasion ; the maximum proportionate increase in the clozapine groups was significantly greater than in the haloperidol groups. The extracellular dopamine level in the basolateral amygdala was significantly elevated after conditioned fear stress. Both clozapine and haloperidol suppressed this dopamine fear response. Suppression of fear response of dopamine by clozapine and haloperidol suggests that these antipsychotic agents affect the mechanism of dopamine release, at least in the amygdala.

阿立哌唑和氟哌啶醇同样抑制恐惧条件大鼠细胞外多巴胺水平的显着增加，而氟哌啶醇增加而阿立哌唑降低基础多巴胺水平。抗精神病药的作用会减弱杏仁核的多巴胺恐惧反应，调节基础多巴胺水平。氟哌啶醇和氯氮平均显着增加杏仁核基底外侧核的基础多巴胺水平，且呈剂量相关性。氯氮平组的最大比例增加显着大于氟哌啶醇组。条件性恐惧应激后，基底外侧杏仁核的细胞外多巴胺水平显着升高。氯氮平和氟哌啶醇都能抑制这种多巴胺恐惧反应。氯氮平和氟哌啶醇抑制多巴胺的恐惧反应表明这些抗精神病药物影响多巴胺释放的机制，至少在杏仁核中。

项目成果

Aripiprazole and haloperidol suppress excessive dopamine release in the amygdala in response to conditioned fear stress, but show contrasting effects on basal dopamine release in methamphetaminesensitized rats.

阿立哌唑和氟哌啶醇可抑制杏仁核响应条件性恐惧应激而过度释放多巴胺，但对甲基苯丙胺致敏大鼠的基础多巴胺释放显示出相反的作用。

• 发表时间: 2009
• 作者: Oshibuchi H; Inada K; Sugawara H; Ishigooka J
• 通讯作者: Ishigooka J

Difference in effect of haloperidol and aropiprazole on excessive release of dopamine in the amygdala induced by conditioned fear stress in methamphetamine-sensitized rats.

氟哌啶醇和阿罗哌唑对甲基苯丙胺致敏大鼠条件性恐惧应激引起的杏仁核多巴胺过度释放的影响差异。

• 发表时间: 2008
• 作者: Oshibuchi H; Sugawara H; Inada K; Ishigooka J
• 通讯作者: Ishigooka J

The effect of antipsychotic agents to enhancement of release of dopamine in the amygdala induced by conditioned fear stress; in vivo microdialysis study.

抗精神病药物对条件性恐惧应激引起的杏仁核多巴胺释放的增强作用；

• 发表时间: 2009
• 作者: Oshibuchi H; Inada K; Sugawara H; Ishigooka J
• 通讯作者: Ishigooka J

The effect of clozapine to enhancement of release of dopamine in the amygdala induced by conditioned fear stress; in vivo microdialysis study.

氯氮平增强条件性恐惧应激引起的杏仁核多巴胺释放的作用；

• 发表时间: 2008
• 作者: Oshibuchi H; Inada K; Sugawara H; Ishigooka J
• 通讯作者: Ishigooka J

Action of amygdala dopamine and effect of antipsychotics.

杏仁核多巴胺的作用和抗精神病药物的作用。

• 发表时间: 2010
• 作者: Oshibuchi H; Inada K; Ishigooka J
• 通讯作者: Ishigooka J