Wolff Mary C, Leander J David
Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, Mail Code No. 0510, Indianapolis, IN 46285, USA.
Psychopharmacology (Berl). 2003 Aug;168(4):410-6. doi: 10.1007/s00213-003-1449-3. Epub 2003 Apr 23.
The cognitive impairments evident in many schizophrenics are related to the severity of their negative symptoms and ability to function in society. Drugs that alleviate cognitive impairments, in addition to other psychotic symptoms, may have an important influence on treatment outcome and the course of the illness.
A delayed non-match to sample task conducted in an eight-arm radial maze was used to determine the influence of four atypical antipsychotics (olanzapine, ziprasidone, risperidone, and clozapine), as well as a typical neuroleptic (haloperidol) on consolidation processes in healthy rats.
Well-trained rats were required to recall after a 7-h delay where they had received food pellets during an information phase (first four arm choices) in order to obtain the remaining food pellets during a retention phase (second four arm choices).
The total number of errors that occurred during the retention session increased with increasing delay periods from 0 to 7 h. When administered orally immediately after the information phase, olanzapine (3 and 5 mg/kg) and risperidone (0.1 mg/kg) significantly reduced the number of errors made during the retention phase. Under the same conditions, clozapine, ziprasidone and haloperidol failed to affect the total number of retention phase errors.
Some atypical antipsychotics, such as olanzapine and risperidone, improve consolidation processes and may alleviate the cognitive impairments associated with schizophrenia.
许多精神分裂症患者明显存在的认知障碍与他们阴性症状的严重程度以及社会功能相关。除缓解其他精神病性症状外,能减轻认知障碍的药物可能对治疗结果和疾病进程有重要影响。
采用在八臂放射状迷宫中进行的延迟非匹配样本任务,以确定四种非典型抗精神病药物(奥氮平、齐拉西酮、利培酮和氯氮平)以及一种典型抗精神病药物(氟哌啶醇)对健康大鼠巩固过程的影响。
训练有素的大鼠需要在延迟7小时后回忆在信息阶段(前四次臂选择)中获得食物颗粒的位置,以便在保留阶段(后四次臂选择)获得剩余的食物颗粒。
在保留阶段出现的错误总数随着延迟时间从0小时增加到7小时而增加。在信息阶段后立即口服给药时,奥氮平(3和5毫克/千克)和利培酮(0.1毫克/千克)显著减少了保留阶段出现的错误数量。在相同条件下,氯氮平、齐拉西酮和氟哌啶醇未能影响保留阶段错误的总数。
一些非典型抗精神病药物,如奥氮平和利培酮,可改善巩固过程,并可能减轻与精神分裂症相关的认知障碍。