Risperidone and ritanserin but not haloperidol block effect of dizocilpine on the active allothetic place avoidance task
Risperidone and ritanserin but not haloperidol block effect of dizocilpine on the active allothetic place avoidance task
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DOI：
10.1073/pnas.0711273105
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发表时间：
2008-01-22
影响因子：
11.1
通讯作者：
Vales, Karel
中科院分区：
文献类型：
--
作者：
Bubenikova-Valesova, Vera;Stuchlik, Ales;Vales, Karel
精神分裂症患者的空间工作记忆或短期位置记忆受损。抗精神病药物，特别是典型的抗精神病药物，对精神分裂症认知功能障碍的有效性仍然存在争议。抑制5-羟色胺（5-HT）2A/2C受体对抗精神病药治疗的精神分裂症患者认知改善很重要。本工作的目的是建立5-HT 2A/2C受体拮抗剂ritanserin的作用，（2.5或5 mg/kg），多巴胺D2拮抗剂氟哌啶醇（0.1或1 mg/kg）和非典型抗精神病药利培酮（0.1 mg/kg或1 mg/kg），其是5-HT 2A/2C和D2受体的拮抗剂，对地佐环平（MK-801，0.1 mg/kg）亚慢性给药诱导的认知缺陷的影响。我们使用了主动的异位位置回避（AAPA）任务，要求大鼠区分相关和不相关的刺激，在某种程度上类似于精神分裂症患者的信息处理干扰中断。我们的研究结果表明，5-HT 2A/2C受体拮抗剂治疗，无论其对D2受体的影响，阻断MK-801产生的认知障碍。氟哌啶醇不能充分减少MK-801诱导的AAPA缺陷。有趣的是，利培酮和氟哌啶醇单独给药，而不是利坦色林，在完整的大鼠AAPA性能受损。在精神分裂症样行为的动物模型中，利坦色林和利培酮实际上独立于它们对自发活动的影响而改善认知。这一发现与某些抗精神病药物主要对精神分裂症认知功能障碍有效的假设一致。
Spatial working memory or short-term place memory is impaired in schizophrenia. The efficiency of antipsychotic drugs, particularly of typical antipsychotics, on cognitive deficit in schizophrenia remains disputable. Inhibition of serotonin (5-HT) 2A/2C receptors is important for cognitive improvement in schizophrenic patients treated with antipsychotics. The aim of the present Work was to establish the effect of the 5-HT2A/2C receptor antagonist ritanserin (2.5 or 5 mg/kg), the dopamine D2 antagonist haloperidol (0.1 or 1 mg/kg), and the atypical antipsychotic risperidone (0.1 mg/kg or 1 mg/kg), which is an antagonist of both 5-HT2A/2C and D2 receptors, on cognitive deficit induced by subchronic administration of dizocilpine (MK-801, 0.1 mg/kg). We used the active allothetic place avoidance (AAPA) task, requiring the rat to differentiate between relevant and irrelevant stimuli, in a way similar to disruption of information processing disturbed in schizophrenic patients. Our results show that treatment with 5-HT2A/2C receptor antagonists, regardless of their effect on D2 receptors, blocked the cognitive impairment produced by MK-801. Haloperidol did not sufficiently reduce the deficit in AAPA induced by MK-801. Interestingly, administration of risperidone and haloperidol alone, but not ritanserin, impaired the AAPA performance in intact rats. Ritanserin and risperidone actually improve cognition independently of their effect on locomotor activity in an animal model of schizophrenia-like behavior. This finding is in accordance with the assumption that some antipsychotics are primarily effective against cognitive dysfunction in schizophrenia.