Nagai Taku, Murai Rina, Matsui Kanae, Kamei Hiroyuki, Noda Yukihiro, Furukawa Hiroshi, Nabeshima Toshitaka
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Psychopharmacology (Berl). 2009 Jan;202(1-3):315-28. doi: 10.1007/s00213-008-1240-6. Epub 2008 Aug 6.
Cognitive deficits, including memory impairment, are regarded as a core feature of schizophrenia. Aripiprazole, an atypical antipsychotic drug, has been shown to improve disruption of prepulse inhibition and social interaction in an animal model of schizophrenia induced by phencyclidine (PCP); however, the effects of aripiprazole on recognition memory remain to be investigated.
In this study, we examined the effect of aripiprazole on cognitive impairment in mice treated with PCP repeatedly.
Mice were repeatedly administered PCP at a dose of 10 mg/kg for 14 days, and their cognitive function was assessed using a novel-object recognition task. We investigated the therapeutic effects of aripiprazole (0.01-1.0 mg/kg) and haloperidol (0.3 and 1.0 mg/kg) on cognitive impairment in mice treated with PCP repeatedly.
Single (1.0 mg/kg) and repeated (0.03 and 0.1 mg/kg, for 7 days) treatment with aripiprazole ameliorated PCP-induced impairment of recognition memory, although single treatment significantly decreased the total exploration time during the training session. In contrast, both single and repeated treatment with haloperidol (0.3 and 1.0 mg/kg) failed to attenuate PCP-induced cognitive impairment. The ameliorating effect of aripiprazole on recognition memory in PCP-treated mice was blocked by co-treatment with a dopamine D1 receptor antagonist, SCH23390, and a serotonin 5-HT1A receptor antagonist, WAY100635; however, co-treatment with a D2 receptor antagonist raclopride had no effect on the ameliorating effect of aripiprazole.
These results suggest that the ameliorative effect of aripiprazole on PCP-induced memory impairment is associated with dopamine D1 and serotonin 5-HT1A receptors.
认知缺陷，包括记忆障碍，被视为精神分裂症的核心特征。阿立哌唑，一种非典型抗精神病药物，已被证明可改善苯环己哌啶（PCP）诱导的精神分裂症动物模型中的前脉冲抑制破坏和社交互动；然而，阿立哌唑对识别记忆的影响仍有待研究。
在本研究中，我们检查了阿立哌唑对反复接受PCP治疗的小鼠认知障碍的影响。
小鼠以10mg/kg的剂量反复给予PCP，持续14天，并使用新物体识别任务评估其认知功能。我们研究了阿立哌唑（0.01 - 1.0mg/kg）和氟哌啶醇（0.3和1.0mg/kg）对反复接受PCP治疗的小鼠认知障碍的治疗效果。
阿立哌唑单次（1.0mg/kg）和反复（0.03和0.1mg/kg，持续7天）治疗可改善PCP诱导的识别记忆障碍，尽管单次治疗显著缩短了训练期间的总探索时间。相比之下，氟哌啶醇（0.3和1.0mg/kg）单次和反复治疗均未能减轻PCP诱导的认知障碍。阿立哌唑对PCP处理小鼠识别记忆的改善作用被多巴胺D1受体拮抗剂SCH23390和5-羟色胺5-HT1A受体拮抗剂WAY100635联合治疗所阻断；然而，D2受体拮抗剂雷氯必利联合治疗对阿立哌唑的改善作用没有影响。
这些结果表明，阿立哌唑对PCP诱导的记忆障碍的改善作用与多巴胺D1和5-羟色胺5-HT1A受体有关。
